CN102309495A - Composite preparation and preparing method thereof - Google Patents
Composite preparation and preparing method thereof Download PDFInfo
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- CN102309495A CN102309495A CN2010102132929A CN201010213292A CN102309495A CN 102309495 A CN102309495 A CN 102309495A CN 2010102132929 A CN2010102132929 A CN 2010102132929A CN 201010213292 A CN201010213292 A CN 201010213292A CN 102309495 A CN102309495 A CN 102309495A
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- tamsulosin
- dutasteride
- compound preparation
- piller
- preparation
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Abstract
The invention relates to a composite preparation, and preparing method and use thereof. The composite preparation uses Tamsulosin and Dutasteride as active ingredients, wherein Tamsulosin is in the form of enteric pellet, granule or tablet, Dutasteride is in the form of soft capsule, and both of them are filled in a hard capsule. The invention discloses a preparing method of the composite preparation.
Description
Technical field
The present invention relates to a kind of compound preparation and method for preparing, belong to medical technical field.
Background technology
(benign prostatic hyperp1asia BPH) is the commonly encountered diseases of elderly men to benign prostatic hyperplasia, and sickness rate increased progressively with the age, and clinical symptoms is not necessarily arranged when still the hypertrophy pathological changes being arranged.The influence that receives many factors of BPH, like smoking, obesity, drink, race, heredity, hypertension, diabetes, sexual life, socioeconomic status etc., though various factors is had more research, the definite relation that they and BPH take place is confirmed yet.The sickness rate of BPH is mainly from autopsy data, and 50 years old male has 40%, 80 years old has 90% BPI-I Histological change is arranged.There are every year 1700000 patients BPH to go outpatient service to go to a doctor approximately in the U.S., about 300,000 People's Bank of China's operation on prostate, annual because of BPH melts about 2,000,000,000 dollars, this shows that BPH brings white elephant for society, family and patient.
Multiple drug treatment is used to attempt treatment BPH, but only has two kinds of methods to be widely accepted:
1. suppress the stimulation of androgen to the prostate growth; The antiandrogen treatment often makes medicament: finasteride, dutasteride, epristeride etc., and the cause of disease of BPH possibly be multifactor property, but two existence that the most basic condition is aged and testis.BPH does not take place in the preadolescence castration; Castration can be disturbed the principle of the pathological process androgen suppression therapy BPH of BPH to derive from the observed prostatic growth of embryo is depended on dihydrotestosterone (dihydrotestosterone; DHT) existence, DHT is transformed under the effect of 5-alpha-reductase by testosterone.2. the tension force that suppresses prostate and bladder neck smooth muscle.The medicine that often uses: terazosin, Tamsulosin and alfuzosin/doxazosin.The research prompting of BPH cellular change, prostatic increase is mainly caused by the hypertrophy of a matter, and causes blocking of efferent tract with two kinds of different modes: the firm static that the lump that is 1. formed by hamartoplasia causes is blocked; 2. by comprise neck of bladder, prostatic smooth muscle tissue between matter and capsula prostatica shrink the dynamic property that causes and block.The tension force of being regulated by sympathetic nerve has by inference constituted 40% of neck of bladder resistance to flow output, and this also is the inherent mechanism that produces and use alpha-blocking agent treatment BPH.
Tamsulosin hydrochloride is a high selectivity alpha-1 adrenergic receptor antagonist; α-1A receptor acting to mainly being distributed in prostate and the peripheral smooth muscle tissue thereof is the strongest, and α-1D receptor takes second place, a little less than the α-1B effect that mainly is distributed in blood vessel wall; Can reduce the pressure of back urethra; Increase the urine flow rate, reduce residual urine amount, blood pressure is not almost had influence.Rapid-action, side reaction is low, relapse rate is low.The research that the U.S.'s two big medical centres are used these article (dosage is 0.4mg or 0.8mg) treatment 1488 routine BPH patients shows that curative effect of these article and safety are all good.Can increase the urine flow rate, reduce residual urine volume, improve IPSS scoring and quality of life.These article side effect incidence rate is extremely low, and dizzy have generation with the idol of feeling sick, but all can tolerate.
The dutasteride is a kind of synthetic 4-nitrogen steroid hormone chemical compound.This is one type of new special inhibitor of 5, and it can irreversibly suppress testosterone is metabolized to stronger androgen dihydrotestosterone of imitating.These article are used to treat benign prostatic hyperplasia, and the prostate of increase is dwindled, and improve urine stream and improve the symptom that benign prostatic hyperplasia brings.
Clinical experiment shows that the dutasteride can make weight of prostate reduce the heavy burdens, and increases Qmax, alleviates patient's symptom, and liver function and sexual function are not had tangible influence, and good safety and toleration are arranged, and is the ideal medicine of treatment benign prostatic hyperplasis.
Tamsulosin hydrochloride is a high selectivity alpha-1 adrenergic receptor antagonist, and the dutasteride is one type of new special inhibitor of 5, and it can irreversibly suppress testosterone is metabolized to stronger androgen dihydrotestosterone of imitating.Because the target of hormone therapy is to reduce prostatic volume, and the purpose of alpha-blocking agent treatment is to reduce the tension force of matter and peplos between prostate, these two kinds of Therapeutic Method is combined to use increase clinical efficacies obviously have very big temptation.Therefore both couplings have good synergism.Has the exploitation meaning.
Summary of the invention
Technology described in the invention relates to field of medicaments, is meant that specifically with Tamsulosin, dutasteride be compound preparation of active component and preparation method thereof.
Tamsulosin of the present invention and dutasteride's compound preparation, its active component Tamsulosin comprises its various pharmaceutical salts, free alkali and solvate, example hydrochloric acid salt, tartrate, benzene sulfonate, succinate etc., preferred salt hydrochlorate.
The amount that each preparation unit contains the active component dutasteride is 0.05～5mg, is preferably 0.1～1mg, and the amount that contains the active component Tamsulosin is 0.04～4mg.Be preferably 0.1～1mg.Both preferred compound doses are dutasteride 0.5mg, Tamsulosin 0.4mg.
Wherein, Tamsulosin can be enteric coated tablet or piller.The dutasteride is dissolved in the appropriate solvent and adds suitable antioxidant and is prepared into soft capsule.Tamsulosin is prepared into medicine carrying piller or tablet with suitable material through proper method, wraps up suitable enteric coating then.The two mixes with proper proportion, fills in the hard capsule.
The solvent that wherein is used to dissolve the dutasteride includes but not limited to suffering/capric acid monoglyceride, suffering/capric acid diglyceride, glyceryl monostearate, and one or more mixture.Its antioxidant is oil-soluble antioxidant, includes but not limited to butylated hydroxyarisol (BHA), and the tert-butyl group is to hydroxy-methylbenzene (BHT), vitamin E.
The ball core material that is used to prepare the Tamsulosin piller includes but not limited to sucrose, lactose, Icing Sugar, starch, microcrystalline Cellulose.Enteric coating material mainly comprises one or more in ethyl cellulose and aqueous dispersion thereof, stearic acid, cellulose acetate phthalate ester, the crylic acid resin (like RS100, RL100, RS 30D, RL30D, NE30D).The hard capsule meaning cellulose substances that is used for last filling is main material but not gelatin glycerol, and its main material is HPMC.
Compound preparation of the present invention can be used for moderate or severe benign prostatic hyperplasia and reduces the risk of its concurrent acute urinary retention, and can be used for moderate or the operation of severe benign prostatic hyperplasia.
The specific embodiment
Come compound preparation of the present invention and preparation method thereof done further specifying through following instance, but be not limited in following instance.
Embodiment 1 compound recipe Tamsulosin dutasteride capsule
Prescription:
Dutasteride's part:
The capsule shells part:
Technology:
1. get gelatin, glycerol, titanium dioxide, ferrum oxide (Huang) purified water is put in the water-bath heating and is made fusing, and stirs, and with medium chain triglyceride, and the medium chain triglyceride that contains lecithin (0.3%) is lubricant, the preparation soft capsule shell.
2. get decanoyl/octanoyl glycerides and put and be heated to 40 ℃ in the water-bath, and in container, fill nitrogen,, add BHT and dutasteride, make dissolving fully, be transparent and homogeneous liquid to carry out next step.Be cooled to 25 ℃-33 ℃.Filter, subsequent use.
3. prepare the medicine carrying soft capsule with above-mentioned capsule material and medicinal liquid.About 66mg in every softgel shell, the heavily about 100mg of its content.Obtain medicine carrying dutasteride soft capsule.
The Tamsulosin part:
| Supplementary material | Inventory |
| Tamsulosin hydrochloride | 0.4g |
| Microcrystalline Cellulose | 211.253 |
| Refined gram is suitable | 55.01 |
| Purified water | In right amount |
Technology:
1. get tamsulosin hydrochloride and microcrystalline Cellulose, pulverize, cross 60 sieves, with equivalent incremental method mix homogeneously.With purified water system soft material, 24 mesh sieves are granulated, and wet granular is joined in the centrifugal granulator, adopt centrifugal granulation to prepare the medicine carrying piller.
2. get the enteric coating powder---refined gram is suitable, is scattered in the purified water, and concentration is about 20%, and this coating solution is wrapped in above-mentioned medicine carrying piller surface through fluid bed, and the coating weightening finish is about 20%.Obtain Tamsulosin medicine carrying enteric piller.
The merging of two kinds of medicines:
Above-mentioned dutasteride's soft capsule that obtains and Tamsulosin medicine carrying enteric piller are filled in the HPMC hard capsule, make every hard capsule contain dutasteride 0.5mg, Tamsulosin 0.4mg.
Embodiment 2 compound recipe Tamsulosin dutasteride capsules
Prescription:
Dutasteride's part:
The capsule shells part:
Technology:
1. get gelatin, glycerol, titanium dioxide, ferrum oxide (Huang) purified water is put in the water-bath heating and is made fusing, and stirs, and with medium chain triglyceride, and the medium chain triglyceride that contains lecithin (0.3%) is lubricant, the preparation soft capsule shell.
2. get decanoyl/octanoyl glycerides and put and be heated to 40 ℃ in the water-bath, and in container, fill nitrogen,, add BHT and dutasteride, make dissolving fully, be transparent and homogeneous liquid to carry out next step.Be cooled to 25 ℃-33 ℃.Filter, subsequent use.
3. prepare the medicine carrying soft capsule with above-mentioned capsule material and medicinal liquid.About 66mg in every softgel shell, the heavily about 100mg of its content.Obtain medicine carrying dutasteride soft capsule.
The Tamsulosin part:
| Supplementary material | Inventory |
| Tamsulosin hydrochloride | 0.4g |
| Microcrystalline Cellulose | 211.253 |
| Refined gram is suitable | 55.01 |
| Purified water | In right amount |
Technology:
1. get tamsulosin hydrochloride and microcrystalline Cellulose, pulverize, cross 60 sieves, with equivalent incremental method mix homogeneously.With purified water system soft material, 24 mesh sieves are granulated, 60 ℃ of oven dry, 24 order granulate.
2. get the enteric coating powder---refined gram is suitable, is scattered in the purified water, and concentration is about 20%, and this coating solution is wrapped in above-mentioned medicine carrying particle surface through fluid bed, and the coating weightening finish is about 20%.Obtain Tamsulosin medicine carrying enteric coated particles.
The merging of two kinds of medicines:
Above-mentioned dutasteride's soft capsule that obtains and Tamsulosin medicine carrying enteric coated particles are filled in the HPMC hard capsule, make every hard capsule contain dutasteride 0.5mg, Tamsulosin 0.4mg.
Embodiment 3 compound recipe Tamsulosin dutasteride capsules
Prescription:
Dutasteride's part:
The capsule shells part:
Technology:
1. get gelatin, glycerol, titanium dioxide, ferrum oxide (Huang) purified water is put in the water-bath heating and is made fusing, and stirs, and with medium chain triglyceride, and the medium chain triglyceride that contains lecithin (0.3%) is lubricant, the preparation soft capsule shell.
2. get decanoyl/octanoyl glycerides and put and be heated to 40 ℃ in the water-bath, and in container, fill nitrogen,, add BHT and dutasteride, make dissolving fully, be transparent and homogeneous liquid to carry out next step.Be cooled to 25 ℃-33 ℃.Filter, subsequent use.
3. prepare the medicine carrying soft capsule with above-mentioned capsule material and medicinal liquid.About 66mg in every softgel shell, the heavily about 100mg of its content.Obtain medicine carrying dutasteride soft capsule.
The Tamsulosin part:
| Supplementary material | Inventory |
| Tamsulosin hydrochloride | 0.4g |
| Microcrystalline Cellulose | 211.253 |
| Magnesium stearate | 1.0g |
| Refined gram is suitable | 55.01 |
| Purified water | In right amount |
Technology:
1. get tamsulosin hydrochloride and microcrystalline Cellulose, pulverize, cross 60 sieves, with equivalent incremental method mix homogeneously.With purified water system soft material, 24 mesh sieves are granulated, 60 ℃ of oven dry, 24 order granulate.Add the magnesium stearate mix homogeneously, with φ 3mm punch die compacting microplate.
2. get the enteric coating powder---refined gram is suitable, is scattered in the purified water, and concentration is about 20%, and this coating solution is wrapped in above-mentioned microplate surface through fluid bed, and the coating weightening finish is about 20%.Obtain Tamsulosin medicine carrying enteric microplate.
The merging of two kinds of medicines:
Above-mentioned dutasteride's soft capsule that obtains and Tamsulosin medicine carrying enteric microplate are filled in the HPMC hard capsule, make every hard capsule contain dutasteride 0.5mg, Tamsulosin 0.4mg.
Claims (9)
1. a compound preparation is characterized in that, wherein active component is Tamsulosin and dutasteride, and wherein Tamsulosin comprises its various pharmaceutical salts, free alkali and solvate, example hydrochloric acid salt, tartrate, benzene sulfonate, succinate etc., preferred salt hydrochlorate.
2. the compound preparation of claim 1, the amount that described each preparation unit contains the active ingredient dutasteride is 0.05～5mg, is preferably 0.1～1mg, the amount that contains the active component Tamsulosin is 0.04～4mg.Be preferably 0.1～1mg.Both preferred compound doses are dutasteride 0.5mg, Tamsulosin 0.4mg.
3. the described arbitrary compound preparation of claim 1～3 is characterized in that, Tamsulosin can be enteric coated tablet or piller.
4. the described arbitrary compound preparation of claim 1～4 is characterized in that, the dutasteride is dissolved in the appropriate solvent and adds suitable antioxidant and is prepared into soft capsule.Tamsulosin is prepared into medicine carrying piller or tablet with suitable material through proper method, wraps up suitable enteric coating then.The two mixes with proper proportion, and is encapsulated.
5. the described compound preparation of claim 4 is characterized in that, the solvent that is used to dissolve the dutasteride includes but not limited to hot capric acid monoglyceride, hot capric acid diglyceride, glyceryl monostearate, and one or more mixture.Its antioxidant is oil-soluble antioxidant, includes but not limited to butylated hydroxyarisol (BHA), and the tert-butyl group is to hydroxy-methylbenzene (BHT), vitamin E.
6. the described compound preparation of claim 4 is characterized in that, the ball core material that is used to prepare the Tamsulosin piller includes but not limited to sucrose, lactose, Icing Sugar, starch, microcrystalline Cellulose.
7. the described compound preparation of claim 4; It is characterized in that the enteric coating material that is used for preparing the Tamsulosin piller mainly comprises one or more of ethyl cellulose and aqueous dispersion thereof, stearic acid, cellulose acetate phthalate ester, crylic acid resin (like RS100, RL100, RS 30D, RL30D, NE30D).
8. the described compound preparation of claim 4 is characterized in that, the hard capsule meaning cellulose substances that is used for last filling is main material but not gelatin glycerol, and its main material is HPMC.
9. the described compound preparation of claim 2～8 can be used for moderate or severe benign prostatic hyperplasia and reduces the risk of its concurrent acute urinary retention, and can be used for moderate or the operation of severe benign prostatic hyperplasia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102132929A CN102309495A (en) | 2010-06-30 | 2010-06-30 | Composite preparation and preparing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102132929A CN102309495A (en) | 2010-06-30 | 2010-06-30 | Composite preparation and preparing method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN102309495A true CN102309495A (en) | 2012-01-11 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102132929A Pending CN102309495A (en) | 2010-06-30 | 2010-06-30 | Composite preparation and preparing method thereof |
Country Status (1)
| Country | Link |
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| CN (1) | CN102309495A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102247379A (en) * | 2011-01-12 | 2011-11-23 | 北京润德康医药技术有限公司 | Compound preparation and preparation method thereof |
| CN103479595A (en) * | 2012-06-13 | 2014-01-01 | 成都国弘医药有限公司 | Dutasteride-containing soft capsule |
| CN104069084A (en) * | 2013-03-25 | 2014-10-01 | 重庆华邦制药有限公司 | Dutasteride soft capsule with stable quality |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1646135A (en) * | 2002-04-24 | 2005-07-27 | 贝林格尔英格海姆法玛两合公司 | Pharmaceutical combination for the treatment of benign prostatic hyperplasia or for the long-term prevention of acute urinary retention |
| CN1758903A (en) * | 2003-01-27 | 2006-04-12 | 安斯泰来制药有限公司 | Enteric sustained-release fine particles for tamsulosin or its salt and process for producing the same |
-
2010
- 2010-06-30 CN CN2010102132929A patent/CN102309495A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1646135A (en) * | 2002-04-24 | 2005-07-27 | 贝林格尔英格海姆法玛两合公司 | Pharmaceutical combination for the treatment of benign prostatic hyperplasia or for the long-term prevention of acute urinary retention |
| CN1758903A (en) * | 2003-01-27 | 2006-04-12 | 安斯泰来制药有限公司 | Enteric sustained-release fine particles for tamsulosin or its salt and process for producing the same |
Non-Patent Citations (1)
| Title |
|---|
| 朱建英等: "《良性前列腺增生治疗药》", 《世界临床药物》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102247379A (en) * | 2011-01-12 | 2011-11-23 | 北京润德康医药技术有限公司 | Compound preparation and preparation method thereof |
| CN103479595A (en) * | 2012-06-13 | 2014-01-01 | 成都国弘医药有限公司 | Dutasteride-containing soft capsule |
| CN103479595B (en) * | 2012-06-13 | 2015-08-26 | 成都国弘医药有限公司 | A kind of soft capsule containing dutasteride |
| CN104069084A (en) * | 2013-03-25 | 2014-10-01 | 重庆华邦制药有限公司 | Dutasteride soft capsule with stable quality |
| CN104069084B (en) * | 2013-03-25 | 2019-06-25 | 重庆华邦制药有限公司 | A kind of dutasteride's soft capsule that quality is stable |
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| PB01 | Publication | ||
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Application publication date: 20120111 |