CN105878998A

CN105878998A - Pharmaceutical preparation for hyperplasia of prostate

Info

Publication number: CN105878998A
Application number: CN201610360714.2A
Authority: CN
Inventors: 林祥宇; 郭增光; 杜玲杰
Original assignee: SHANDONG KERNEL AND HALL PHARMACEUTICAL INDUSTRY Co Ltd
Current assignee: Tong Ren Pharmaceutical Co., Ltd.
Priority date: 2016-05-29
Filing date: 2016-05-29
Publication date: 2016-08-24

Abstract

The invention relates to a pharmaceutical preparation for hyperplasia of prostate. The pharmaceutical preparation is prepared from the following raw materials: 2.5kg of finasteride, 9.2kg of starch, 9.2kg of pregelatinized starch, 13.5kg of lactose, 11.6kg of microcrystalline cellulose, 2.5kg of sodium carboxymethyl starch, 25kg of 2% hydroxypropyl methylcellulose pulp and 0.15kg of magnesium stearate; and the raw materials are granulated by a conventional method to prepare 500,000 tablets. The product provided by the invention realizes an obvious and stable treatment effect on hyperplasia of prostate and has a broad application prospect.

Description

Pharmaceutical preparation for hyperplasia of prostate

Technical field

The invention belongs to technical field of pharmaceuticals, concrete, relate to a kind of pharmaceutical preparation for hyperplasia of prostate.

Background technology

Hyperplasia of prostate is the common frdquently encountered disease of serious harm human health, and is incremented by with the age；And Chinese patients is close to 100,000,000 people, it it is the disease in serious harm human physical and mental health and life-span.Along with progress of human society, aged tendency of population is on the rise, and the sickness rate of BPH is raising year by year.According to statistics, 60～the old people of 69 years old in severe BPH prevalence up to 50%～60%, the range of age is 70～old people's prevalence then up to more than 80% of 80 years old.Study of incident mechanism about prostatic hyperplasia is a lot of, but the cause of disease the most still fails to illustrate, and the chief complaint of prostatic hyperplasia has following symptom: 1, frequent micturition, frequent micturition is early symptom, first increases for nocturia number of times, but urine volume is few every time.During lower urinary tract obstruction, the patient of 50%～80% has urgent micturition or urge incontinence.Detrusor of bladder lose compensatory after, there is chronic urinary retention, the available capacity of bladder thus reduce, the interval between micturition time more shortens.If with vesical calculus or infection, then frequent micturition is further obvious, and with dysurea.2, dysuria, body of gland increases, and mechanical obstruction increases the weight of, and finds dysuria symptom, and the degree of lower urinary tract obstruction is not directly proportional to body of gland size.Owing to urethral resistance increases, controlled micturition is initial to be delayed, and urination time extends, and range is not far, and urine line is thin and unable.Urine bifurcated, has vesical tenesmus to feel.Increasing the weight of further as blocked, patient must increase abdominal pressure to help to urinate.Breathing makes abdominal pressure increase and decrease, and occurs that uroflow is interrupted and dripping.Residual urine is that detrusor of bladder loses compensatory result.When residual urine volume is very big, and bladder excessive expands and pressure is the highest, and higher than urethral resistance, urine and stool is overflowed from urethra voluntarily, claims overflow incontinence.After nighttime sleep, pelvic diaphragm muscle relaxes, and urine is more easy to flow out voluntarily, enuresis nocturna occurs.Some patients residual urine at ordinary times is few, but suffering from cold, drink, suppress urine, drug administration or when having other reasons to cause sympathetic activation, acute urinary retention can occur suddenly.The symptom of Urinary retention can fashion time bad.Some patients can be acute urinary retention be onset symptoms.3, hematuria, on prostate mucosa, capillary injection and thin vessels are expanded and are subject to increase the tractive of body of gland or rub with bladder, when bladder contraction, can cause under mirror or gross hematuria.

Finasteride is the conventional Western medicine preparation for treating prostatic hyperplasia, and finasteride be one 4-aza steroid, and it is the specific inhibitor that testosterone metabolism becomes the desmoenzyme-II type 5a-reductase during higher dihydrotestosterone.And benign prostatic hyperplasia or in referred to as prostate hyperplasia depends on prostate testosterone to the conversion of dihydrotestosterone.This medicine can effectively reduce blood and intraprostatic dihydrotestosterone.Finasteride does not has affinity to androgen receptor.Finasteride belongs to 5 alpha reductase inhibitors, and it is by its mechanism of hormone, i.e. suppression testosterone changes into dihydrotestosterone (DHT), makes prostate volume reduce and improves symptom, increases uroflow speed, preventing benign prostatic hyperplasia (BPH) progress.

But, clinical research shows, use the male patient of finasteride treatment have >=there is the following untoward reaction relevant with medication in the people of 1%: hyposexuality (finasteride 1.8%, placebo 1.3%) and sexual impotence (finasteride 1.3%, placebo 0.7%).Additionally, male patient has 0.8% appearance ejaculation amount to reduce, placebo group 0.4%.After stopping the only treatment of guarantor's method, these untoward reaction disappear, and have detected the finasteride impact on ejaculation amount in another study, find and placebo zero difference.After finasteride listing, the adverse events of report also includes breast tenderness or enlargement, anaphylaxis (including erythra, pruritus, urticaria and lip swelling) and testicular pain.

Western medicine makes it apply to be restricted owing to there is the reason such as untoward reaction and Drug tolerance, and although western medical treatment prostatic hyperplasia took effect at that time, but easily must not recur after drug withdrawal and effect a radical cure, and Patients with Prostatic Hyperplasia is it is generally required to Long-term taking medicine, it is easily generated a series of toxic and side effects, elderly patients are made to be difficult to bear, and somewhat expensive.Operative treatment narrow application range, risk is high；No operation interventional therapy equipment limits, and costly.By contrast, Chinese medicine treatment prostatic hyperplasia has the theory of uniqueness of controlling oneself, have accumulated rich experience, hyperplasia of prostate belongs to the category of " difficulty in urination " of Chinese medicine, the dysuria that its main pathogenesis is kidney and bladder qi dysfunction causes, wherein with dysuria, drop and be short of, patient's condition relatively do not delay person be referred to as " infirmity "；Inaccessible with urine, drop completely without, the more anxious person of patient's condition is referred to as " closing ".The name of the difficulty in urination, head sees "Nei Jing", and the discussion of summary made by the sick position of the difficulty in urination, pathogenesis by this book, such as " Plain Questions specimen disease passes an opinion piece " meaning: " the urinary bladder disease, anuria "；" Ling Shu Miraculous Pivot or Divine Axis this most defeated " cloud: " three Jiao persons ... reality person's constipation and anuria, void then incontinence of urine, incontinence of urine then mends it, and constipation and anuria then rushes down it." the sick position of the difficulty in urination at bladder, but and kidney, spleen, lung three Jiao all have close relationship, its treatment should be conceived to lead to according to the principle of " the six hollow viscera must keep its unobstructed ".Chinese medicine, with the nontoxic superiority of its reliable curative effect and low toxicity, has caused attracting attention of common people, and therefore, Chinese medicine prostatic hyperplasia has broad prospects.

Prior art prescriptions of Chinese medicine lacks dialectical, and treatment cycle is long, and property is not strong to the ill, and curative effect is inconspicuous, the most also can bring side effect to patient, increase patient suffering, finds effective, safe drugs, it has also become the problem generally needing to solve from natural drug.

Summary of the invention

The present invention is with reference to motherland's medical science understanding pathogenetic to prostatic hyperplasia and the invaluable experience for the treatment of, refering to existing reasonable formula, determination for the treatment of based on pathogenesis obtained through differentiation of symptoms and signs, according to Chinese Pharmacopoeia and pharmacology compatibility, pushing away Chen Zhixin gain, determination for the treatment of based on pathogenesis obtained through differentiation of symptoms and signs is always the core theory of Chinese medicine disease, how to take into account secondary pathogenesis for main pathogenesis medication simultaneously, take into account the treatment of general character and individual character, thus at utmost embody intension and the extension of Chinese traditional treatment disease, be a realistic problem of Chinese patent medicine compatibility.Theoretical by Chinese medical discrimination, the Etiological pathogenesis causing this disease is that Shi Re Bing Pian drives in the wrong direction, so that stationing the part of the body cavity below the umbilicus, housing the bladder, kidneys and bowels, hinders in meridians.Inventor is by the research to Chinese medicine, and combines dialectical demonstration, in many ways collects the length of many families, seek therapeutic regimen, from motherland's medical treasure-house, filter out stomach warming aproll, open lung qi dispersing gas, promoting diuresis with drugs of tasteless flavour, draws turbid going out, the natural component of wind dispelling cold expelling, by theory of Chinese medical science prescription, skim the cream off milk, be meticulously configured to the compound recipe finasteride tablet of the present invention in conjunction with Traditional Chinese Medicine technology, relative to Western medicine, obvious to Treatment of Benign Prostatic Hyperplasia effect, stable, useful men's health.

For realizing the object of the invention, the technical solution used in the present invention is as follows:

For the pharmaceutical preparation of hyperplasia of prostate, it is prepared by following raw material:

Finasteride 1.2kg, medicinal herb components 1.3kg, starch 9.2kg, pregelatinized Starch 9.2kg, lactose 13.5kg, microcrystalline Cellulose 11.6kg, carboxymethyl starch sodium 2.5kg, 2%(mass fraction) hypromellose slurry 25kg, magnesium stearate 0.15kg, take above-mentioned raw materials, conventionally pelletize, prepare 500,000, tablet.

Described medicinal herb components, is prepared by following raw material:

Ramulus Cinnamomi, the Rhizoma Anemarrhenae, Radix Rehmanniae Preparata, Semen Vaccariae, Fructus Ligustri Lucidi, Herba Epimedii, Rhizoma Zingiberis Recens, Herba Lysimachiae, Semen Armeniacae Amarum, Pericarpium Zanthoxyli, Rhizoma Curcumae, Semen Cuscutae, Herba Taraxaci, Olibanum, Lignum Aquilariae Resinatum, Semen Plantaginis, Fructus Forsythiae, Cortex Phellodendri, Radix Achyranthis Bidentatae, Fructus Schisandrae Chinensis, Herba Schizonepetae, Rhizoma Dioscoreae, Herba Houttuyniae,

Spina Gleditsiae, Radix Puerariae, Herba Artemisiae Scopariae, Rhizoma Atractylodis, Radix Glycyrrhizae, Radix Ophiopogonis, Pericarpium Citri Reticulatae.

Preferably, described medicinal herb components, the raw material of following weight it is prepared:

Ramulus Cinnamomi 40 parts, the Rhizoma Anemarrhenae 40 parts, 40 parts of Radix Rehmanniae Preparata, Semen Vaccariae 35 parts, Fructus Ligustri Lucidi 35 parts,

Herba Epimedii 35 parts, 35 parts of Rhizoma Zingiberis Recens, Herba Lysimachiae 35 parts, 30 parts of Semen Armeniacae Amarum, 30 parts of Pericarpium Zanthoxyli,

Rhizoma Curcumae 30 parts, Semen Cuscutae 30 parts, Herba Taraxaci 28 parts, Olibanum 28 parts, Lignum Aquilariae Resinatum 28 parts,

Semen Plantaginis 28 parts, Fructus Forsythiae 25 parts, Cortex Phellodendri 25 parts, Radix Achyranthis Bidentatae 25 parts, Fructus Schisandrae Chinensis 25 parts,

Herba Schizonepetae 25 parts, Rhizoma Dioscoreae 20 parts, Herba Houttuyniae 20 parts, Spina Gleditsiae 20 parts, Radix Puerariae 20 parts,

Herba Artemisiae Scopariae 20 parts, Rhizoma Atractylodis 15 parts, 15 parts of Radix Glycyrrhizae, Radix Ophiopogonis 10 parts, Pericarpium Citri Reticulatae 10 parts.

The preparation method of described medicinal herb components is:

1) each crude drug is weighed, standby；

2) take Rhizoma Zingiberis Recens, Rhizoma Dioscoreae, Radix Glycyrrhizae slow fire fry 8 minutes, pulverized 90 mesh sieves, prepared composition A;

3) take Ramulus Cinnamomi, Radix Rehmanniae Preparata, Semen Vaccariae, Herba Epimedii, Herba Lysimachiae, Pericarpium Zanthoxyli, Herba Taraxaci, Lignum Aquilariae Resinatum, Semen Plantaginis, Fructus Schisandrae Chinensis, Herba Schizonepetae, Herba Houttuyniae, Herba Artemisiae Scopariae, Radix Ophiopogonis put into container, add the distilled water of 4 times amount, after soaking 1 hour, boil 2 hours, extract decoction liquor；Again add 3 times amount distilled water, boil 1 hour, extract decoction liquor；Finally, add 2 times amount distilled water, heated and boiled 1 hour, extract decoction liquor；Merging three decoction liquor, be condensed into the extractum that density is 1.3g/ml, 60 DEG C dried, pulverizes prepared composition B；

4) take surplus stock and add 3 times of weight 70%(volume ratios) ethanol, reflux, extract, 2 times, each 1 hour, extracting solution merged, and is concentrated into the extractum that density is 1.3g/ml, and 60 DEG C are dried, pulverize prepared composition C；

5) it is uniformly mixed into point A, B, C and get final product.

Each 1 (containing finasteride 2.4mg), every day 1 time, (medicine) being taken before meal with or take with food simultaneously.

The component of medicine of the present invention reduces the composition proportion of finasteride, the every pure western medicine composition content reducing 60%, has been greatly reduced the many side effect caused due to finasteride.Herbal component all uses natural raw material of Chinese medicine, it prepares simplicity, medicine source is extensive, with low cost, it follows the prescriptions principle of the traditional Chinese medical science, and all medicines share, bring out the best in each other, monarch respectively executes its effect, and the compound preparation of the present invention can promote that prostate volume reduces, and effectively alleviates bladder outlet obstruction (BOO) symptom；And energy and blood of human body and the five internal organs physiological function are had coordinated balance effect, regulating functional activities of qi, reach the purpose for the treatment of must aim at the pathogenesis of disease.Be applicable to middle-aging male prostatic hyperplasia, frequent micturition that hypertrophy causes, urgent micturition, urine thin line, acraturesis, dribbling, urine wait, urinary incontinence, urine retention, the person that needs operative treatment or because health other reasons can not operator

Detailed description of the invention

Embodiment 1

Finasteride 1.2kg, medicinal herb components 1.3kg, starch 9.2kg, pregelatinized Starch 9.2kg, lactose 13.5kg, microcrystalline Cellulose 11.6kg, carboxymethyl starch sodium 2.5kg, 2% hypromellose slurry 25kg, magnesium stearate 0.15kg, take above-mentioned raw materials, conventionally pelletize, prepares 500,000, tablet.

Described medicinal herb components, is prepared by the raw material of following weight:

The preparation method of described medicinal herb components is:

1) each crude drug is weighed, standby；

5) it is uniformly mixed into point A, B, C and get final product.

Embodiment 2

Pathology is tested

The impact of testosterone propionate induction castrated rats prostatic hyperplasia model

Laboratory animal Wistar rat, male, body weight 120-150 gram, 40, etherization descending castration art (extracts testis) under sterile working, within postoperative 3 days, select rat 30 in good condition, be randomly divided into model group, matched group, experimental group.Separately taking rat 10, operation process is the same, but does not extract testis, as a control group (sham operated rats).

Medication is administered with dose of test drug oral (gavage), and matched group (sham operated rats) and model group give same volume distilled water, and experimental group gives the compound recipe finasteride tablet of embodiment 1 preparation, and matched group gives commercially available finasteride tablet.It is administered once a day, successive administration 21 days.During this period, in addition to sham operated rats, once, dosage is 25mg kg to other 3 treated animal subcutaneous injection testosterone propionate injection every other day^-1Body weight, is administered latter 24 hours in last, puts to death rat, clip rat prostate, cut off deferent duct, urethra and bladder etc., weigh prostatic weight in wet base with trace electronics Libra at body of gland after weighing record body weight.By the wet tissue weight (mg) that weighs divided by body weight (in units of 100 grams), calculate prostate weight in wet base coefficient.Then being placed on 10% formalin solution to fix, conventional dehydration is transparent, paraffin section, dyeing, tissues observed metamorphosis under optical microscope.Choose 5 prostate tube chambers under mirror, under image processor, measure wall of the lumen thickness (1am) and lumen diameter (um) respectively.

Data process in units of group, calculate each treated animal prostate average weight in wet base coefficient respectively, relatively each treated animal prostate weight in wet base coefficient.The significance test t of group difference checks.Result such as table 1 below:

Table 1

Show that the prostatic hyperplasia model that testosterone propionate is induced by medicine of the present invention improves significantly than matched group and model group.

Embodiment 3

Collect the out-patient of 79 example hyperplasia of prostates, age 33-60 year, the course of disease 1-12 month.It is randomly divided into: treatment group 40 example, matched group 39 example.Two groups of data such as age, the state of an illness there was no significant difference, and has comparability.

Diagnosis basis

With reference to " Chinese medicine disease Standardization of diagnosis and curative effect "

Start frequent micturition, especially nocturia increased frequency, gradually have a dysuria, remaining drown endless, time serious, can have urine retention or urinary incontinence.

Primary disease is more common in elderly men.

Rectal touch: essence room is loose, smooth surface and without tuberosity, clear-cut margin, medium hardness and full of elasticity, Rolandic fissure shoals or disappears.

Ultrasound diagnosis: prostate size measurement compared with normal increases, bladder residual urine is more than 60 milliliters.

Test method

Matched group gives commercially available finasteride tablet, each 1 (containing finasteride 5mg), every day 1 time, (medicine) being taken before meal with or take with food simultaneously.

Experimental group give embodiment 1 preparation compound recipe finasteride tablet, each 1 (containing finasteride 2.4mg), every day 1 time, (medicine) being taken before meal with or take with food simultaneously.

Criterion of therapeutical effect and therapeutic outcome

Criterion of therapeutical effect

The industry standard " Chinese medical disease Standardization of diagnosis and curative effect " promulgated with reference to State Administration of Traditional Chinese Medicine, for hyperplasia of prostate efficacy evaluation:

Cure: unobstructed micturition, prostatic examination is obviously reduced, without residual urine.

Taking a turn for the better: symptom of urinating takes a turn for the better, residual urine reduces.

Do not heal: symptom and every inspection are all without improving.

Treatment statistical result is shown in Table 2.

Table 2

Group	Number of cases	Cure	Take a turn for the better	Do not heal	Total effective rate
						Treatment group	40	22	14	4	90%
Matched group	39	16	13	10	74.3%

Treatment group relatively matched group significant difference.

Listed above is only the optimal specific embodiment of the present invention.It is clear that the invention is not restricted to above example, it is also possible to there are many deformation.All deformation that those of ordinary skill in the art can directly derive from present disclosure or associate, are all considered as protection scope of the present invention.

Claims

1., for the pharmaceutical preparation of hyperplasia of prostate, it is prepared by following raw material:

Finasteride 2.5kg, starch 9.2kg, pregelatinized Starch 9.2kg, lactose 13.5kg, microcrystalline Cellulose 11.6kg, carboxymethyl starch sodium 2.5kg, 2% hypromellose 25kg, magnesium stearate 0.15kg, take above-mentioned raw materials, conventionally pelletize, prepare 500,000, tablet.

2., for the pharmaceutical preparation of hyperplasia of prostate, it is prepared by following raw material:

Finasteride 1.2kg, medicinal herb components 1.3kg, starch 9.2kg, pregelatinized Starch 9.2kg, lactose 13.5kg, microcrystalline Cellulose 11.6kg, carboxymethyl starch sodium 2.5kg, 2% hypromellose 25kg, magnesium stearate 0.15kg, take above-mentioned raw materials, conventionally pelletize, prepare 500,000, tablet.

Pharmaceutical preparation the most according to claim 2, it is characterised in that described medicinal herb components is prepared by the crude drug of following weight:

4. according to the pharmaceutical preparation described in claim 2-3, it is characterised in that the preparation method of described medicinal herb components is:

1) each crude drug is weighed, standby；

2) Rhizoma Zingiberis Recens, Rhizoma Dioscoreae, Radix Glycyrrhizae are taken, mixing, fry 8 minutes with slow fire, pulverized 90 mesh sieves, prepared composition A；

3) Ramulus Cinnamomi, Radix Rehmanniae Preparata, Semen Vaccariae, Herba Epimedii, Herba Lysimachiae, Pericarpium Zanthoxyli, Herba Taraxaci, Lignum Aquilariae Resinatum, Semen Plantaginis, Fructus Schisandrae Chinensis, Herba Schizonepetae, Herba Houttuyniae, Herba Artemisiae Scopariae, Radix Ophiopogonis are taken, mixing, put into container, add the distilled water of 4 times of weight, after soaking 1 hour, boil 2 hours, extract decoction liquor；Again add the distilled water of 3 times of weight, boil 1 hour, extract decoction liquor；Finally, add 2 times of weight distilled water, heated and boiled 1 hour, extract decoction liquor；Merging three decoction liquor, be condensed into the extractum that density is 1.3g/ml, 60 DEG C dried, pulverizes prepared composition B；

4) take surplus stock medicine, mixing, add 3 times of weight 70%(volume ratios) ethanol, reflux, extract, 2 times, each 1 hour, extracting solution merged, and is concentrated into the extractum that density is 1.3g/ml, and 60 DEG C are dried, pulverizing prepared composition C；

5) it is uniformly mixed into point A, B, C and get final product.

5. the medicinal application of pharmaceutical preparation described in claim 1-4.