CN1785226A

CN1785226A - Phyllanth soft capsule and its prepn. method

Info

Publication number: CN1785226A
Application number: CN 200510022063
Authority: CN
Inventors: 杜彦军
Original assignee: Individual
Current assignee: Individual
Priority date: 2005-11-14
Filing date: 2005-11-14
Publication date: 2006-06-14

Abstract

A softgel of phylianthus urinaria is prepared from the extract of phylianthus urinaria and the dispersing medium in weight ratio of (0.1-2): 1 through preparing the core substance, preparing shell substance, and die pressing.

Description

Blattbulume soft capsule and processing technology thereof

Affiliated field

The present invention relates to a kind of medicine soft capsule and processing technology, particularly blattbulume soft capsule and processing technology thereof.

Background technology

Cacumen Securinegae Suffruticosae (Phyllanthus urinaria L.) is the herb of Euphorbiaceae Leafflower Phyllanthus L., record the earliest in " the SHENGCAO property of medicine is wanted fully ", effect with calming liver and clearing heat, promoting diuresis to remove toxic substance is used for the treatment of enteritis, dysentery, urinary tract infection, innominate toxic swelling etc.Domestic scholars is isolated 10 chemical compounds altogether from the dry herb of Cacumen Securinegae Suffruticosae, comprising n-octadecane, cupreol, ellagic acid, daucosterol, kaempferol, Quercetin, gallic acid, globulariacitrin, dehydrogenation chebulic acid methyl ester and Methy Brevifolin-carboxlate.

Hepatitis B is called for short hepatitis B again, and it is to be caused by hepatitis B virus, by blood and body fluid communication, has the infectious disease of chronic carrier state.A most important risk of hepatitis B just is that it develops into chronic hepatitis and liver cirrhosis easily, and the minority case can change primary hepatoma into.Hepatitis B is one of infectious disease of serious threat human health, is classified as the ninth-largest disease that causes death in the whole world by World Health Organization (WHO) at present.It is reported that annual have 1,000,000 people to die from the disease relevant with hepatitis B approximately.Data shows that the whole world has 2,000,000,000 people to be subjected to the infection of hepatitis virus approximately, and wherein 3.5 hundred million people become the chronic carrier of hepatitis B virus, and the carrier more than 75% is lived in the Asian-Pacific area.The data show of China's Ministry of Public Health in August, 2003 announcement, by the end of the year 2002, total chronic hepatitis B patient more than 2,000 ten thousand examples in the whole nation account for 1.57% of population; The hepatitis B virus surface antigen carrying rate is up to 9.8%, number about 1.2 hundred million.There are every year 280000 people to die from hepatopathy approximately, account for 3.65% in the national death toll.Hepatitis B virus be 1964 found, in after this more than 40 year, the shade that it has become countless people can't get rid of.Therefore, effectively treat chronic viral hepatitis B, reduce hepatitis b virus infection ratio and become our task of top priority.

Though the research of treatment hepatitis B medicine and Hepatitis B virus vaccine gets along with at present, does not still have good specific drug so far.The treatment of hepatitis B is mainly adopted antiviral, immunomodulating and is improved Comprehensive Treatments such as liver function, and wherein antiviral therapy, especially combination antiviral therapy have become the key link for the treatment of hepatitis B.Antiviral drugs still is first-selected with the interferon.Interferon has antiviral and immune dual regulation effect, can comparatively fast improve clinical symptoms and sign, recover the normal hepatocytes function, part suppresses or removes viral, curative effect of its treatment chb is very sure and generally acknowledged, but owing to cost an arm and a leg, side effect is many, usually recur after the drug withdrawal and be difficult to promote the use of.Nucleoside analog has become " favorite " on the hepatitis medicament market in recent years, such drug main will suppress archaeal dna polymerase (HBV-DNAP), and to other virus replication intermediate, very little as super coiled DNA (cccDNA) effect, so virus replication can restart from cccDNA after the drug withdrawal, thereby cause the generation of " knock-on " phenomenon.

Make powder capsule and treat 37 routine HBsAg carriers since India scholar Thyagarajan etc. reported Phyllanthusamarus (phyllanthus amarus) herb in 1988 on " lancet " magazine, negative conversion rate flavor 59%, and matched group only is 4%, 10 examples are followed up a case by regular visits in 37 examples did not have 1 example sun commentaries on classics in 6 months, obtained since the challenging therapeutic outcome the domestic research heat that has occurred subsequently phyllanthus plant.Through the effort of scholar in all parts of the country and country's eight or five tackling key problem groups, the research of Cacumen Securinegae Suffruticosae has obtained very big progress, has affirmed effect and the hepatoprotective activity of the anti-HBV of Cacumen Securinegae Suffruticosae.Because clinical HBeAg of Cacumen Securinegae Suffruticosae and HBV-DNA negative conversion rate height, can improve patient's clinical symptoms, recovery normal hepatocytes function, and low price, few side effects, can take for a long time, especially can bring into play the obvious synergistic effect and have irreplaceable advantage with interferon, nucleoside analog and immunomodulator use in conjunction, in the medicine of present clinical treatment chb, occupy important one seat.

The modern pharmacological research result shows that Cacumen Securinegae Suffruticosae extract is external all to have good inhibitory effect to HBV mark HBsAg, HBeAg; Can obviously suppress the statement of artificial challenge's DHB surface antigen in the duckling body; Can obviously alleviate the acute liver damage of carbon tetrachloride induced mice, rat, show that Cacumen Securinegae Suffruticosae has tangible anti-HBV effect and hepatoprotective activity.Yang Lingling published an article on " Chinese Medicine " traditional medicine version in 2005 to introduce when first Chinese medicine hepatopathy that China holds is is at present prevented and treated high-rise forum and the seminar of China pearl grass (Cacumen Securinegae Suffruticosae) medical science and writes: " Military Medical Science Institute screens 21 kinds of Chinese herbal medicine with anti-HBV potentiality with the hepadnavirus model, found that only the Herba Phyllanthi Urinariae extract has stronger inhibitory action to duck HBV; Sino-Japanese Friendship Hospital, Chinese Academy of Sciences's biotechnology research associating have been carried out in the body and external two antivirus tests to the Herba Phyllanthi Urinariae extract, find that the Herba Phyllanthi Urinariae extract has significant deactivation to HBV, to the specific inhibitory effect of having duplicated of viral gene HBV-DNA." (seeing " Chinese Medicine " 2005.6.16A7 version)

Summary of the invention

Purpose of the present invention promptly is to overcome the shortcoming of prior art, provides a kind of good airproof performance, content of dispersion accurate, blattbulume soft capsule that precision is high and processing technology thereof, and its cost is low, output is high, reduces the stimulation of medicine to patient's gastrointestinal tract, and can reduce pollution.

Purpose of the present invention is achieved through the following technical solutions: blattbulume soft capsule, it is made up of following components in part by weight, Cacumen Securinegae Suffruticosae extract: disperse medium=0.1-2: 1.

The blattbulume soft capsule processing technology, preparation content: get Cacumen Securinegae Suffruticosae, after clean system, be ground into coarse powder, add the alcohol heating reflux secondary, Cacumen Securinegae Suffruticosae: ethanol=1-2: 3-16, the time is 2 hours to reflux for the first time, time is 1 hour for the second time, filter merging filtrate, decompression recycling ethanol and to be concentrated into relative density be 1.10 clear paste, temperature is 50 ℃, and is standby; Residue adds 6 times of water gagings and decocted 3 hours, filter, it is 1.10 that filtrate decompression is concentrated into relative density, and temperature is 50 ℃, adds above-mentioned clear paste, mixing, spray drying gets dry extract, gets extract powder, and be 0.1-2 by extract powder with the disperse medium weight ratio: 1 mixes, on colloid mill, ground 20-60 minute, can make uniform liquid;

The preparation soft capsule shell: get gelatin, glycerol, water, chocolate brown pigment, ratio is a gelatin: glycerol: water: chocolate brown pigment=1.0: 0.4-0.6: 1.0-1.4: 0.005, take by weighing in above ratio, in the addingization glue bucket, 60 ℃ were stirred 4 hours, placed 6-8 hour, the degassing, standby.

Compacting: the sizing material bucket of insulation is connected with capsule machine, capsular content is put into hopper,, select to roll mould No. 10 according to the content loading amount, it is as follows to regulate the pelleting parameter: glue box temperature: 50-52 ℃, sprinkler body temperature: 38-40 ℃, adhesive tape thickness: 0.8mm rolls mould rotating speed: 1.8r/min, regulate loading amount, the tolerant heavy 0.60g of every intragranular controls content uniformity well, and in the pelleting process, at any time detect, the soft capsule that extrudes through pellet press is sent in the rotating cage, blows a cold wind over while rotating, and typing is dry, the soft capsule that typing is finished is contained in pallet and is shakeout, continue drying at 25 ℃, with 95% ethanol soft capsule remained on surface liquid is cleaned, promptly.

Disperse medium is a vegetable oil.

Spray drying into and out of tower pathogenic wind-warm technological parameter is: advance 160 ℃～180 ℃ of tower pathogenic wind-warm, go out 80 ℃～90 ℃ of tower pathogenic wind-warm.

By top narration as can be seen, the present invention has the following advantages: make soft capsule and saved adjuvants such as a large amount of sucrose; Soft capsule good airproof performance, content of dispersion are accurate, and the precision height reduces the stimulation of medicine to patient's gastrointestinal tract.Its good looking appearance of soft capsule dosage form, be convenient to swallow, can satisfy different patients' clinical application custom, select for clinical patients provides a medication, processing technology is easy to operation, and cost is low, output is high, and can reduce pollution.

The specific embodiment

The present invention will be further described below in conjunction with embodiment:

Embodiment:

Get Cacumen Securinegae Suffruticosae 2000g, be ground into coarse powder, add the alcohol heating reflux secondary, measured 2 hours for 6 times for the first time, measured 1 hour for 6 times for the second time, filter, merging filtrate, decompression recycling ethanol also is concentrated into the clear paste that relative density is 1.10 (50 ℃), and is standby; Residue adds 6 times of water gagings and decocted 3 hours, filters, and it is 1.10 (50 ℃) that filtrate decompression is concentrated into relative density, adds above-mentioned clear paste, mixing, and spray drying gets dry extract, with soybean oil 300g mixing, grinds 40 minutes, can make uniform liquid; Spray drying into and out of tower pathogenic wind-warm technological parameter is: advance 170 ℃ of tower pathogenic wind-warm, go out 90 ℃ of tower pathogenic wind-warm.

Take by weighing gelatin 10kg, glycerol 4kg, water 10kg, pigment 50g, in the addingization glue bucket, 60 ℃ were stirred 4 hours, placed 6-8 hour, and the degassing, standby.

The sizing material bucket of insulation is connected with capsule machine, capsular content is put into hopper,, select to roll mould No. 10 according to the content loading amount, it is as follows to regulate the pelleting parameter: glue box temperature: 50 ℃, the sprinkler body temperature: 38 ℃, adhesive tape thickness: 0.8mm rolls mould rotating speed: 1.8r/min, regulate loading amount (the tolerant heavy 0.60g of every intragranular), control content uniformity well, and in the pelleting process, detect at any time.The soft capsule that extrudes through pellet press is sent in the rotating cage, blows a cold wind over while rotating, and typing is dry, the soft capsule that typing is finished is contained in the rustless steel pallet and is shakeout, continue drying at 25 ℃, soft capsule remained on surface liquid is cleaned, make 1000 of soft capsules with 95% ethanol.

The clinical research result shows, the oral Cacumen Securinegae Suffruticosae capsule of 135 routine chb patients, and 4/time, 3 times/day, serve on three months, the negative conversion rate of HBeAg and HBV-DNA is respectively 59.0% and 65.4%, is significantly higher than 14.0% and 17.4% of MIEAOLING JIAONANG matched group.Interferon and Cacumen Securinegae Suffruticosae drug combination, the negative conversion rate of HBeAg is 44.4%, with single similar with interferon (40%), but HBV-DNA negative conversion rate, HBeAg and HBV-DNA simultaneously negative conversion rate drug combination group (44.4%, 38.9%) all apparently higher than single with interferon group (30%, 30%).Lamivudine and 12 week and 24 weeks of Cacumen Securinegae Suffruticosae drug combination, HBeAg negative conversion rate drug combination group (27.91%, 39.53%) is apparently higher than single lamivudine group (7.69%, 12.82%) of using.Thymosin treatment chb is after three months, HBsAg, HBeAg and anti--HBe-IgM negative conversion rate are respectively 4.7%, 31% and 60%, use the Cacumen Securinegae Suffruticosae sheet to be respectively 14.3%, 63.8% and 66% and unite, wherein the negative conversion rate drug combination group of HBeAg is apparently higher than single thymosin group of using.Underleaf pearl formulation is clinical to be taken for a long time, and the report of obvious adverse reaction takes place Shang Weijian.

Claims

1, blattbulume soft capsule is characterized in that it is made up of following components in part by weight, Cacumen Securinegae Suffruticosae extract: disperse medium=0.1-2: 1.

2, blattbulume soft capsule processing technology is characterized in that:

Preparation content: get Cacumen Securinegae Suffruticosae, after clean system, be ground into coarse powder, add the alcohol heating reflux secondary, Cacumen Securinegae Suffruticosae: ethanol=1-2: 3-16, the reflux time first time is 2 hours, and the time is 1 hour for the second time, filters, merging filtrate, decompression recycling ethanol and to be concentrated into relative density be 1.10 clear paste, temperature is 50 ℃, and is standby; Residue adds 6 times of water gagings and decocted 3 hours, filter, it is 1.10 that filtrate decompression is concentrated into relative density, and temperature is 50 ℃, adds above-mentioned clear paste, mixing, spray drying gets dry extract, gets extract powder, and be 0.1-2 by extract powder with the disperse medium weight ratio: 1 mixes, on colloid mill, ground 20-60 minute, can make uniform liquid;

The preparation soft capsule shell: get gelatin, glycerol, water, chocolate palm fibre food coloring, ratio is a gelatin: glycerol: water: chocolate brown pigment=1.0: 0.4-0.6: 1.0-1.4: 0.005, take by weighing in above ratio, in the addingization glue bucket, 60 ℃ were stirred 4 hours, placed 6-8 hour, the degassing, standby.

3, blattbulume soft capsule processing technology according to claim 2 is characterized in that: disperse medium is a vegetable oil.

4, blattbulume soft capsule processing technology according to claim 2 is characterized in that: spray drying into and out of tower pathogenic wind-warm technological parameter is: advance 160 ℃～180 ℃ of tower pathogenic wind-warm, go out 80 ℃～90 ℃ of tower pathogenic wind-warm.