CN108324924A - Application of the bitter melon protein in preparing anti-nipple tumor virus infection drug - Google Patents
Application of the bitter melon protein in preparing anti-nipple tumor virus infection drug Download PDFInfo
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- CN108324924A CN108324924A CN201810368038.2A CN201810368038A CN108324924A CN 108324924 A CN108324924 A CN 108324924A CN 201810368038 A CN201810368038 A CN 201810368038A CN 108324924 A CN108324924 A CN 108324924A
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- bitter melon
- virus infection
- melon protein
- drug
- tumor virus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/168—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
Abstract
The invention discloses a kind of application of bitter melon protein in preparing anti-nipple tumor virus infection drug, in particular for preventing the diseases such as the change of cervical epithelial cells tumor, vaginitis, cervical erosion, cervical polyp, cervical carcinoma and the condyloma acuminatum that are caused by human papilloma virus infection.Using a kind of drug containing bitter melon protein provided by the present invention, in anti-human papilloma virus (anti-HPV) (HPV) infection there is unexpected therapeutic effect, anti-HPV viruse effective percentage to reach 90% or more.And balsam pear derives from a wealth of sources, and is easy to plant, integration of drinking and medicinal herbs, without any toxicity and side effects, manufacturing cost are low, use easy to spread.
Description
Technical field
A kind of drug the present invention relates to pharmaceutical preparation application field more particularly to bitter melon protein and containing the albumen exists
Prevent the application in human papilloma virus infection.
Background technology
Human papilloma virus (HPV, human papilloma virus) is a kind of with interpersonal communicable spherical shape DNA
Virus.According to statistics in the venereal disease in the whole world, genital wart caused by HPV infection accounts for 15-20%, and state of the U.S. 2003-2004
Family's health and an investigation result about HPV popularities of nutrient research project show, 14-59 Sui female genital tract
Total infection rate of HPV is 26.8%.Currently, scientist has successfully isolated more than 200 kinds of HPV hypotype, different hypotypes exists not
Same clinical manifestations, are broadly divided into high-risk-type and low risk.Common high-risk-type include HPV-16,18,30,31,33,
35, the hypotypes such as 39,45,51,52,56,58,59 are carcinoma of vulva, prostate cancer, carcinoma of urinary bladder and palace with high-risk HPV relevant disease
Neck cancer etc.；Common low risk includes HPV-6, the hypotypes such as 11,13,32,34,40,42,43,44,53,54, with low risk HPV
Relevant disease is the diseases such as verruca vulgaris, flat wart, plantar wart, condyloma.The HPV-16 and HPV-18 of wherein high-risk-type are to cause women
The main reason for cervical carcinoma, has very strong infectiousness；In China, almost all of cervical carcinoma is all related with infection HPV.Currently,
Therapy for HPV clinical symptoms includes：
(1) physiotherapy cuts off macroscopic knurl and subclinical by operations such as laser, microwave, photodynamic therapies
Infection.But physical therapy is mainly for tumour caused by virus, not from the presence of source elimination virus；
(2) medicinal treatment there is no the special efficacy antiviral drugs for the virus at present；
(3) immunotherapy, including interferon, interleukin, thymic peptide, transfer factor, BCG vaccine, isotretinoin, autovaccine
Deng defect is expensive, stability is poor, treatment procedure is complicated；
(4) vaccine therapy, U.S. FDA have approved 4 valences (6,11,16 and 18 type) HPV epidemic diseases of Merck companies development and production
Seedling GARDASIL, the vaccine for preventing cervical carcinoma and property wart.But it is not wide enough just for fractionated viral hypotype, target group
General (13-26 Sui woman), Effective immune period short (effective time 3-5), expensive etc. are not easy to promote in developing country.
Therefore, it is badly in need of working out the drug of species specificity prevention human papilloma virus infection.
In field of medicaments, there is different pharmacological effects from the active constituent of plant extract, as ribosomal protein is usually big
Amount is present in the various plants such as Curcurbitaceae, Euphorbiaceae, grass family and Caryophyllaceae.Due to its with hypoglycemic, reducing blood lipid, antibacterial,
It is more to adjust immunocompetence, antitumor and resisting HIV (human immunodeficiency virus, HIV) etc.
Kind effect, receives significant attention.Balsam pear is a kind of medical and edible dual purpose plant, fruit bitter cold in nature, with clearing heat and detoxicating, nourishing is strong
And other effects.In recent years, successively purification obtains plurality of active ingredients, such as bitter melon protein MAP30 from balsam pear fruit and seed
(momordica anti-HIV protein of 30kDa) has broad anti-viral activity, right other than anti-HIV-1 virus
Hepatitis B, encephalitis, influenza and adenovirus etc. have apparent inhibiting effect.But there is not also bitter melon protein in prevention human papilloma at present
Research report in terms of viral (HPV) infection.
Invention content
In view of this, the answering in preparing anti-nipple tumor virus infection drug the present invention provides a kind of bitter melon protein
With, solve in the prior art without effectively treat human papilloma virus infection disease in terms of pharmaceutical problems.
One aspect of the present invention provides application of the bitter melon protein in preparing anti-nipple tumor virus infection drug.
Preferably, bitter melon protein molecular weight is 28-30k D.
Preferably, bitter melon protein is bitter melon protein MAP30.
On the other hand a kind of drug containing bitter melon protein is additionally provided for preventing to be caused by human papilloma virus infection
The change of cervical epithelial cells tumor, vaginitis, cervical erosion, cervical polyp, cervical carcinoma and condyloma acuminatum.
Preferably, bitter melon protein weight accounting is 0.05-5% in drug.
Preferably, a kind of anti-nipple tumor virus infection pharmaceutical dosage form containing bitter melon protein is freeze-dried powder, spray, coagulates
Jelly, tablet, pill, ointment and sustained-release preparation etc. need to prepare according to clinical application.
Using a kind of drug containing bitter melon protein provided by the present invention, have in anti-nipple tumor virus infection prominent
The effect gone out, antiviral effective percentage most preferably reach 95% or more.And balsam pear derives from a wealth of sources, bitter melon protein not only can be from balsam pear fruit
Reality or seed are extracted and are obtained by DNA recombinant expression, are easily obtained, production cost is low, use easy to spread.
Specific implementation mode
The principles and features of the present invention are described below, and illustrated embodiment is served only for explaining the present invention, is not intended to
Limit the scope of the present invention.
Bitter melon protein includes mainly purification MCL, α-Charantin, β-Charantin, γ-Charantin, δ-Charantin, ε-hardship
Tens kinds of melon element and MAP30 etc., wherein this experiment are mainly by taking MAP30, α-Charantin, β-Charantin as an example, MAP30 molecular masses
Molecular mass for 30k D, α-Charantin is 29k D；The molecular mass of β-Charantin is 28k D.
Using existing usually used extracting method：Balsam pear pulp or seed are taken, is pulverized, is extracted, is filtered, separation,
Extraction, dialysis purify acquisition by column chromatography and are characterized.
Or use existing usually used recombination method：By coming out the corresponding protein gene cloning in balsam pear, convert
To great expression in Escherichia coli or saccharomycete etc., recombination obtains bitter melon protein.
Existing research shows that bitter melon protein MAP30, α-Charantin, β-Charantin make normal cell nontoxicity without pair
With.
Embodiment one：Using the bitter melon protein MAP30 of balsam pear extraction in the drug for preparing anti-nipple tumor virus infection
Application, include the following steps：By the bitter melon protein MAP30 0.5g of the freeze-drying of existing method extraction, magnesium stearate 79.5g, carboxylic
Methylcellulose 200g, microcrystalline cellulose 720g, which are thoroughly mixed, obtains anti human papillomavirus medicine D-MAP30, makes every gram
Contain bitter melon protein MAP30 0.1% in drug.
Lysate uses aqua sterilisa and glucose chlorohexidene (glucose chlorohexidene content for 0.15%), using preceding and anti-human
Papillomatosis cytotoxic drug is used in compounding.
Embodiment two：α-the Charantin extracted using balsam pear prepares the freeze dried powder of anti-nipple tumor virus infection, including
Following steps：α-Charantin 0.5g, magnesium stearate 79.5g, carboxymethyl cellulose 200g, microcrystalline cellulose 720g are sufficiently stirred
Mixing obtains anti human papillomavirus medicine D- α-Charantin.
Embodiment three：β-the Charantin extracted using balsam pear prepares the freeze dried powder of anti-nipple tumor virus infection, including
Following steps：β-Charantin 0.5g, magnesium stearate 79.5g, carboxymethyl cellulose 200g, microcrystalline cellulose 720g are sufficiently stirred
Mixing obtains anti human papillomavirus medicine D- β-Charantin.
Example IV：Example IV and embodiment one are difference lies in bitter melon protein MAP30 is added without, only by magnesium stearate
80g, carboxymethyl cellulose 200g, microcrystalline cellulose 720g, which are sufficiently stirred, obtains D-sample.
Embodiment five：The bitter melon protein MAP30 extracted using balsam pear prepares the gelling agent of anti-nipple tumor virus infection, takes
Carbomer is added bitter melon protein MAP30 50g, 2g glucose chlorohexidenes and is added water to triethanolamine tune PH 5.5 while stirring
1000mL constant volumes, it is about 5% to make bitter melon protein MAP30 mass concentrations, is stirred evenly, and is dispensed to get gelling agent N-MAP30.
Embodiment six：The measurement of anti-nipple tumor virus infection drug prepared by embodiment one to five to cytotoxicity
Bitter melon protein D-MAP30, D- α-Charantins, D- β-Charantin, the D- respectively prepared by above-described embodiment one to four
Sample freeze-dried powders drug, bitter melon protein N-MAP30 gelling agents carry out cytotoxicity experiment, it was demonstrated that it does not influence normal cell
Growth.In addition through animal vaginal mucomembranous irritant test, Skin allergy test, mutagenesis and reproductive toxicity test, it was demonstrated that be
Safety, there is no irritation, without finding skin allergic reaction, there is no mutagenicity to chromosome and to jenny life to vagina
Growing ability does not influence.
Embodiment seven：Utilize D-MAP30, D- α-Charantins, D- β-Charantin, D-sample freeze dried powders, bitter melon protein
N-MAP30 gelling agents are respectively in the clinical application for preventing high-risk HPV positive patients
Method：HPV positive patients high-risk to 100 carry out being randomly divided into 5 groups, and freeze-dried drug and lysate are pressed 1:6 ratios
Uterus neck is administered to using vagina injector after example mixing, first group uses bitter melon protein D-MAP30+ lysates；Second group
Use D- α-Charantin freeze-dried powder+lysate of equivalent；Third group uses D- β-Charantin+lysate；4th group directly uses
Bitter melon protein N-MAP30, the 5th group of D-sample pulvis+lysate prepared using example IV.It uses 1 time daily.Every time 1
The therapeutic effect of high-risk HPV positive patient is observed in branch (0.5 gram), administration after 3 months, examined according to patient's subjective symptoms, gynaecology
It looks into and vaginal fluid microscopic examination result, analysis drug falls to the clinical efficacy of high-risk HPV positive patients with virus load
50% or more (including 50%) is effectively (method for detecting virus is using HC2HPV DNA detections), otherwise is invalid, is in addition counted
HPV negative conversion rates, specific data are as shown in table 1.
1 bitter melon protein anti human papillomavirus medicine of table is used to treat the clinic of high-risk HPV positive patients
Effect
| Group | Case load | Effectively | In vain | Efficient (%) | Negative conversion rate |
| First group | 20 | 19 | 1 | 95 | 70 |
| Second group | 20 | 15 | 5 | 75 | 55 |
| Third group | 20 | 12 | 8 | 60 | 55 |
| 4th group | 20 | 15 | 5 | 75 | 60 |
| 5th group | 20 | 8 | 12 | 40 | 15 |
As known from Table 1, bitter melon protein anti human papillomavirus medicine is for treating high-risk HPV positive patients, and effective percentage is most
Up to 95%, negative conversion rate reaches 70%.
Embodiment eight：Utilize D-MAP30, D- α-Charantins, D- β-Charantin, D-sample freeze dried powders；N-MAP30 is solidifying
Jelly faces the clinical application of patient in treatment low risk HPV infection respectively
Method：100 genitals patients with condyloma acuminatum (low risk HPV infection patient) are carried out being randomly divided into 6 groups, will be frozen
Dry drug and lysate press 1:Vagina inject administration is used after the mixing of 6 ratios, first group is lyophilized medicine using bitter melon protein D-MAP30
Product+lysate；Drug+lysate is lyophilized in second group of D- α-Charantin using equivalent；Third group is lyophilized using D- β-Charantin
Drug+lysate；4th group uses bitter melon protein N-MAP30；5th group uses D-sample freeze dried powders+lysate.Daily
Once, it is used in conjunction one month, is discontinued 1 week and is checked, analysis drug to genitals patients with condyloma acuminatum (suffer from by low risk HPV infection
Person) clinical efficacy, count DNA negative conversion rates, specific data are as shown in table 1.
2 bitter melon protein anti human papillomavirus medicine of table
Clinical effectiveness for treating low risk HPV infection patient
As known from Table 2, bitter melon protein anti human papillomavirus medicine is for treating low risk HPV infection patient, negative conversion rate
Up to 95%.
In another embodiment, genetic recombination obtain bitter melon protein MAP30 anti-HPV viruse using it is upper have with
Balsam pear extracts the same therapeutic effects of albumen MAP30.
Signified bitter melon protein drug products of the invention include but are not limited to tablet, pill, pulvis, suspension, ointment
Genital tract position directly can be smeared or be sprayed on as needed to agent, gelling agent, spray and sustained-release preparation, when use, grasp
Make simple and convenient, more hommization.
In conclusion using a kind of drug containing bitter melon protein provided by the present invention, in anti-human papilloma virus (anti-HPV)
(HPV) there is unexpected therapeutic effect, anti-HPV viruse high efficiency is up to 95% in infecting.And balsam pear derives from a wealth of sources, medicine
Eat homologous, the protein toxic relative to traditional Chinese medicine extractions such as Phytolacca acinosas is small, and extracting albumen or recombinant protein can apply, manufacturing cost
It is low, it is easy to spread.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
With within principle, any modification, equivalent substitution, improvement and etc. done should be included within the scope of protection of the invention god.
Claims (6)
1. application of the bitter melon protein in preparing anti-nipple tumor virus infection drug.
2. application of the bitter melon protein according to claim 1 in preparing anti-nipple tumor virus infection drug, feature
It is：The bitter melon protein molecular weight is 28-30k D.
3. application of the bitter melon protein according to claim 2 in preparing anti-nipple tumor virus infection drug, feature
It is：The bitter melon protein is MAP30.
4. a kind of anti-nipple tumor virus infection drug containing bitter melon protein is caused for preventing by human papilloma virus infection
The change of cervical epithelial cells tumor, vaginitis, cervical erosion, cervical polyp, cervical carcinoma and condyloma acuminatum.
5. a kind of anti-nipple tumor virus infection drug containing bitter melon protein, it is characterised in that：Bitter melon protein in the drug
Weight accounting is 0.05-5%.
6. a kind of anti-nipple tumor virus infection drug containing bitter melon protein according to claim 5, which is characterized in that
The pharmaceutical dosage form is freeze-dried powder, spray, gelling agent, tablet, pill, ointment and sustained-release preparation.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810368038.2A CN108324924A (en) | 2018-04-23 | 2018-04-23 | Application of the bitter melon protein in preparing anti-nipple tumor virus infection drug |
| CN201910239002.9A CN109821007B (en) | 2018-04-23 | 2019-03-27 | Application of bitter gourd protein in preparing medicine for resisting human papilloma virus infection |
| CN202210125625.5A CN114470156B (en) | 2018-04-23 | 2019-03-27 | Application of alpha-Momordica charantia extract in preparation of anti-human papilloma virus infection drugs |
| CN202210124995.7A CN114404565B (en) | 2018-04-23 | 2019-03-27 | Application of beta-Momordica charantia extract in preparation of anti-human papilloma virus infection drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810368038.2A CN108324924A (en) | 2018-04-23 | 2018-04-23 | Application of the bitter melon protein in preparing anti-nipple tumor virus infection drug |
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| CN108324924A true CN108324924A (en) | 2018-07-27 |
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| CN201810368038.2A Pending CN108324924A (en) | 2018-04-23 | 2018-04-23 | Application of the bitter melon protein in preparing anti-nipple tumor virus infection drug |
| CN201910239002.9A Active CN109821007B (en) | 2018-04-23 | 2019-03-27 | Application of bitter gourd protein in preparing medicine for resisting human papilloma virus infection |
| CN202210124995.7A Active CN114404565B (en) | 2018-04-23 | 2019-03-27 | Application of beta-Momordica charantia extract in preparation of anti-human papilloma virus infection drugs |
| CN202210125625.5A Active CN114470156B (en) | 2018-04-23 | 2019-03-27 | Application of alpha-Momordica charantia extract in preparation of anti-human papilloma virus infection drugs |
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| CN201910239002.9A Active CN109821007B (en) | 2018-04-23 | 2019-03-27 | Application of bitter gourd protein in preparing medicine for resisting human papilloma virus infection |
| CN202210124995.7A Active CN114404565B (en) | 2018-04-23 | 2019-03-27 | Application of beta-Momordica charantia extract in preparation of anti-human papilloma virus infection drugs |
| CN202210125625.5A Active CN114470156B (en) | 2018-04-23 | 2019-03-27 | Application of alpha-Momordica charantia extract in preparation of anti-human papilloma virus infection drugs |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111249439A (en) * | 2020-03-25 | 2020-06-09 | 重庆旭天生物科技有限公司 | anti-HPV biological protein gel and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| IT1229216B (en) * | 1989-03-31 | 1991-07-25 | Italfarmaco Spa | PROTEINS INHIBIT RIBOSOMES AND THEIR DERIVATIVES. |
| US6652861B1 (en) * | 1999-08-26 | 2003-11-25 | New York University | Anti-HIV and anti-tumor peptides and truncated polypeptides of MAP30 |
| CA2560409A1 (en) * | 2006-09-21 | 2008-03-21 | Innovative Life Sciences Corporation | Herbal product comprising cinnamon and bitter melon |
| CN101070342B (en) * | 2007-05-22 | 2010-09-08 | 山西康宝生物制品股份有限公司 | Balsm-pear-seed ribosome inactivated protein and its coding gene and use |
| CN102166353B (en) * | 2010-02-26 | 2015-05-20 | 孙介光 | A spray for treating diseases caused by human papilloma viruses and a preparation method |
| CA2877272A1 (en) * | 2012-06-26 | 2014-01-03 | Biovalence Sdn. Bhd. | Dosage regime of fusion compounds |
| CN103789333B (en) * | 2014-03-05 | 2016-02-24 | 湖北肽洋红生物工程有限公司 | A kind of oral recombination fusion protein TAT-MAP30 and preparation method and application |
| CN104353058B (en) * | 2014-10-14 | 2016-12-07 | 海南森瑞谱生命科学药业股份有限公司 | Pokeweed antiviral protein lyophilized powder complexing agent and preparation method thereof |
| CN104491838B (en) * | 2014-12-19 | 2017-04-19 | 海南森瑞谱生命科学药业股份有限公司 | Anti-HPV (human papillomavirus) gel dressing and preparation method thereof |
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2018
- 2018-04-23 CN CN201810368038.2A patent/CN108324924A/en active Pending
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- 2019-03-27 CN CN201910239002.9A patent/CN109821007B/en active Active
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111249439A (en) * | 2020-03-25 | 2020-06-09 | 重庆旭天生物科技有限公司 | anti-HPV biological protein gel and preparation method thereof |
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| CN109821007A (en) | 2019-05-31 |
| CN114470156A (en) | 2022-05-13 |
| CN109821007B (en) | 2022-03-15 |
| CN114470156B (en) | 2023-10-17 |
| CN114404565B (en) | 2023-09-26 |
| CN114404565A (en) | 2022-04-29 |
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Application publication date: 20180727 |