CN100558383C - The Chinese medicine of treatment human papilloma virus infection - Google Patents
The Chinese medicine of treatment human papilloma virus infection Download PDFInfo
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- CN100558383C CN100558383C CNB2005100682891A CN200510068289A CN100558383C CN 100558383 C CN100558383 C CN 100558383C CN B2005100682891 A CNB2005100682891 A CN B2005100682891A CN 200510068289 A CN200510068289 A CN 200510068289A CN 100558383 C CN100558383 C CN 100558383C
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Abstract
The present invention relates to treat the Chinese medicine of human papilloma virus infection, described Chinese medicine is made by crude drug such as Flos Carthami, Herba Equiseties Hiemalis.Through the research of clinical efficacy and laboratory pharmacodynamics, medicine of the present invention has extremely strong specific destruction human papillomavirus's function, can effectively remove human papillomavirus in the body.
Description
Technical field:
The present invention relates to treat the Chinese medicine of human papilloma virus infection.
Background technology:
Human papillomavirus (Human papilloma virus, be called for short HPV) genus DNA viroid, its biological nature and biological respinse thereof are: be positive 20 bodies, the about 50-55nm of diameter of spherical grain, people are its unique hosts, can cause the mankind's various warts, as verruca vulgaris, verruca plana, plantar wart, periungual wart and genital wart (as condyloma acuminatum) etc., utilize nucleic acid hybridization technique it can be divided into 28 types, different types can cause with a kind of wart, and a kind of wart can be caused by the HPV of a plurality of types.
HPV is the same with HIV (human immunodeficiency virus) (Human Immunodeficiency Virus), self does not have fertility, the breeding of getting a lift among needs embedding people's the DNA, and different with other pathogen is, it does not cause inflammatory reaction, but inspire the propagation of host cell, be the tumprigenicity growth, and can cause the generation of malignant tumor, as skin carcinoma, carcinoma of tongue etc., condyloma acuminatum has 10% canceration rate, and at the end of last century, the chronic infection of having confirmed epithelium of cervix uteri HPV in the world is the cause of disease of cervical cancer.The present tissue culture of HPV is not success as yet, and also not finding can be for the animal pattern of experiment.
The route of infection: HPV is by immediate contagion, and for example condyloma acuminatum mainly is trafficability characteristic contagion, so it plays the effect of adding fuel to the flames in spreading of AIDS.Condyloma acuminatum is maximum a kind of of number in the sexually transmitted disease (STD) of harm society.Because it is tumor sample growth inside and outside genitals, come big inconvenience of Xi and family friction to people's band of living, its caused malignant tumor will cause the people in desperately.
HPV can have a long or short incubation period or carrier state in human body, in this phase, without any clinical symptoms, but be infectious, and becomes the potential source of infection.And cervical cancer appears in the chronic infection of the long-term HPV of cervix uteri at last.
The present medicine that human papilloma virus infection is not also had to kill HPV, prior art can only take to destroy the way of wart body when the various Verrucosis of treatment, as physical methods such as laser, freezing, microwaves, perhaps use medicine corrosion structure such as podophyllin, cantharidin, Bleomycin A5 etc.These methods are the process misery not only, also has wound surface to form, and is difficult for healing, and because of can not kill virus very easily recurring.Therefore, needing a kind of specific, capable of killing virus medicine comes out.
Summary of the invention:
The objective of the invention is to develop a kind of is the medicine of the treatment human papilloma virus infection of active component with Chinese medicine.
The Chinese medicine compound of the treatment human papilloma virus infection of the present invention's exploitation is made by following bulk drugs:
Flos Carthami 6-60, Herba Equiseti Hiemalis 5-100.
The optimum ratio of above-mentioned raw materials medicine is: Flos Carthami 10-60, Herba Equiseti Hiemalis 5-30;
Best proportioning is: Flos Carthami 10, Herba Equiseti Hiemalis 5.
Monarch drug is constant in the above-mentioned compound recipe, can also add other medicines, is combined into multiple prescription, performance effect in various degree.
As adding Rhizoma Cyperi 10-30 part in addition in the above-mentioned compound recipe.
Find that through laboratory and clinical research single Flos Carthami Herba indigoferae Pseudotinctoriae or list used used Herba Equiseti Hiemalis's Herba indigoferae Pseudotinctoriae, and drug effect is preferably also arranged.
In addition, research finds that also when Flos Carthami and Rhizoma Cyperi compatibility, perhaps Herba Equiseti Hiemalis and Rhizoma Cyperi compatibility have also all obtained effect preferably.Its medication ratio is:
Flos Carthami: Rhizoma Cyperi=2: 1, perhaps Herba Equiseti Hiemalis: Rhizoma Cyperi=2: 1
Therefore, treatment human papilloma virus infection medicine of the present invention can have following multiple compatibility mode:
1. Flos Carthami
2. Herba Equiseti Hiemalis
3. Flos Carthami+Herba Equiseti Hiemalis
4. Flos Carthami+Rhizoma Cyperi
5. Herba Equiseti Hiemalis+Rhizoma Cyperi
6. Flos Carthami+Herba Equiseti Hiemalis+Rhizoma Cyperi
From theory of Chinese medical science, Flos Carthami and Herba Equiseti Hiemalis have the merit of vital energy regualting and blood circulation-promoting; From the doctor trained in Western medicine theory, Flos Carthami and Herba Equiseti Hiemalis have the kill virus effect.
Medicine of the present invention can adopt the conventional method of Chinese medicine preparation to be prepared into the preparation of any routine, for example material medicine is pulverized post-treatment and become tablet, pill, or decocting, or extract with alcohol or alcohol-water mixture, condensed water decocting liquid or extracting solution then, the refining Chinese medicine extract that becomes.With extract and the acceptable various carriers of medicine, adjuvant compatibility, the pharmaceutical methods with those skilled in the art's routine is prepared into various preparations.
The dosage form of medicine of the present invention can be various oral agents, as traditional water decoction, concentrated oral liquid, powder, granule, capsule, tablet, electuary etc.Also can make topical agent, comprise Chinese medicine plaster, spirit, ointment, newborn arm agent, liniment, suppository, aerosol etc., use in the part of infecting.
Treatment human papilloma virus infection medicine of the present invention can be used for following disease or patient: condyloma acuminatum, condyloma acuminatum are Ji sex partner, the family members that Qi Mi cut-grafting is touched; Various HPV carriers comprise cervix uteri, urethra HPV carrier; The early stage canceration patient of condyloma acuminatum and cervix uteri; Various common skin warts are as the molluscum contagiosum of verruca vulgaris, periungual wart, plantar wart, verruca plana and poxvirus infection.
Research through clinical efficacy and laboratory pharmacodynamics, medicine of the present invention has extremely strong specific destruction human papillomavirus's (HPV) function, oral administration enters human body, can effectively remove HPV in the body, relapse rate is extremely low, application is not only convenient and simple clinically, does not have misery, and high cure rate and extremely low relapse rate are arranged.
The clinical research of condyloma acuminatum proves, typical condyloma acuminatum patient 89 examples and 8 example process FQ-PCR-HPV detections is turned out to be the observation that male carrier has carried out clinical efficacy, and carried out the research of pharmacodynamics at laboratory.The result shows: 97 examples are cured 95 people, and cure rate 97.95% recurs 2 people, relapse rate 2,1%.Virus carrier 8 people, after treatment, HPV is all cloudy to be changeed, and does not see recurrence through sufficient long term follow-up.At laboratory, having under the condition of positive control, contain in the suspension of HPV, add pharmaceutical after, no matter HPV 6,11 or HPV all can not detect the DNA of HPV again after 16,18,24 hours, illustrate that medicine of the present invention can remove the treatment mechanism of HPV in vivo.Owing to possess the function that to remove HPV in vivo, therefore can not only cure the patient that clinical symptoms is arranged, and to sex partner, the carrier of morbidity and the patient that is in sub-clinical state all can effectively not remove the body inner virus as yet, thereby played the effect of the prevention and the elimination source of infection, significant on epidemiology.
Because the chronic infection of HPV is the major reason of cervical cancer, medicine of the present invention can also play the effect of prevention cervical cancer after removing cervical HPV.
Under study for action, we find that also it also has good effect to other dermatosis and molluscum contagiosum that HPV infects, in addition to because of HPV infects the pernicious tendentiousness disease that causes, also have researching value as the treatment of the CIN of bowenoid papulosis, cervix uteri.
Below be the researchs such as pharmacodynamic study that the present invention carries out, described " the wart poison is clear " refers to Chinese medicine composition of the present invention, the sharp condyloma latum of " AC " finger tip.
The specific embodiment:
The research of embodiment 1 laboratory pharmacodynamics
The experiment medicine: prescription 1 (hereinafter referred to as " the wart poison is clear "), filling a prescription is (weight portion): Flos Carthami: 6, the Herba Equiseti Hiemalis: 3, Rhizoma Cyperi: 2, water decoction.
To contain in the test solution of HPV and add " the wart poison is clear ", regularly detect with the FQ-PCR technology, to investigate its ability of killing to HPV.
1 materials and methods
1.1HPV the source: HPV6,11 takes from untreated patient's AC wart body, it is standby to grind to form tissue homogenate after NS cleans under aseptic condition.HPV 16,18 takes from the cleanout fluid of patient's skin lesion.
1.2 Chinese medicine sample: " the wart poison is clear " and contrast Chinese medicine are made the water decoction identical with clinical practice.(contrast Chinese medicine ingredients: No. 1: Radix Angelicae Sinensis: 30 grams, the Rhizoma Atractylodis Macrocephalae: 15 grams.No. 2: Poria: 30, Radix Glycyrrhizae: 15.)
1.3 key instrument: PE-5700 type quantitative real time PCR Instrument and related computer software.
1.4PCR primer and fluorescent probe: Zhongshan Medical Univ. of the state approval of hanging oneself listing reaches the HPV6,11 that peace gene diagnosis center provides, HPV16,18 type FQ-PCR diagnostic kits, and its sensitivity is 25 copies.
2 experimental techniques
2.1 get AC tissue homogenate or cleanout fluid 0.6ml, add Chinese medicine test sample 2.4ml respectively, control tube then adds NS 2.4ml, under 4 ℃, extracts DNA on time, and feminine gender and positive control pipe are established in each test simultaneously.
2.2FQ-PCR reactions steps: adopt conventional alkaline lysis method of extracting DNA, get 0.2ml adds in the thin-walled reaction tube at every turn, add a certain amount of primer, F-probe, dNTP, archaeal dna polymerase and buffer etc. simultaneously, put into PE-5700 fluorescent PCR instrument, after 93 ℃ of 2min give degeneration, circulate repeatedly 40 times by 93 ℃ of 45s, 55 ℃ of 120s, quantitative result is analyzed automatically by computer software, calculates its initial copy number.
3 results
3.1 test for the first time adds " the wart poison is clear " and promptly can not measure HPV6,11 after 24 hours, and control tube and Chinese medicine control tube still kept original high concentration copy number (table 1) until the 13rd day
Table 1 is result of the test (HPV-6,11) for the first time
| Time | Control tube | No. 1 Chinese medicine control tube | No. 2 Chinese medicine control tube | Wart poison pigging |
| 24hrs | 2.8×10 7 | 5×10 7 | 1.5×10 7 | 0 |
| The 5th day | 1.86×10 6 | 1.97×10 6 | 1.88×10 6 | 0 |
| The 8th day | 5.6×10 7 | 8.2×10 6 | 1.3×10 6 | 0 |
| The 13rd day | 1.6×10 7 | 2.1×10 6 | 5.3×10 6 | 0 |
The 2nd experimental result of table 2 (HPV-6,11)
| Time | Control tube | No. 1 Chinese medicine control tube | No. 2 Chinese medicine control tube | Wart poison pigging |
| 24hrs | 8.9×10 4 | 3.6×10 4 | 1.2×10 4 | 0 |
| 48hrs | 1.56×10 5 | 2.6×10 4 | 1.2×10 5 | 0 |
| The 7th day | 1.4×10 4 | 3.7×10 4 | 2.8×10 5 | 0 |
3 experimental results of table 3 mat woven of fine bamboo strips (HPV-16,18)
| Time | The NS control tube | The clear control tube of wart poison |
| 24hrs | 1.7×10 4 | 0 |
| 72hrs | 6.4×10 4 | 0 |
The result of 3 tests is all consistent, and the repeatable and credible of test is described.Experiment also prove wart poison clear in vitro to HPV-6,11 and HPV-16,18 identical killing effect is all arranged, have the ability that broad-spectrum is killed HPV.
Following having experimental results show that clearly in vitro destroyed differently to HPV-DNA and general chemical biocide non-selectivity ground at the wart poison, but equally with antibiotic etc have a selectivity sterilization functions, we selected HBV in contrast the property advanced investigation.
| Time | Control tube | The HBV developmental tube | Wart poison pigging |
| 24hrs | 3.6×105 | 2.8×105 | 0 |
Evidence ' wart poison clear ' does not have destruction at external DNA to HBV, and HPV-DNA is had tangible destruction, so its effect of killing HPV is specific, and is identical with antibiotic effect.
The clinical research of embodiment 2AC and carrier's 97 examples
1 clinical data
1.1AC 97 examples, male 65 people, women 32 people.Once accept other treatment recurrence before the treatment and those selected amounts to 31 people, accounted for 32.29% of whole AC.
1.2 site of pathological change: add up with the position
Foreskin: 20 examples
Glans penis: 12 examples
Coronary sulcus: 23 examples
Penis: 7 examples
Inside and outside the urethral orifice: 8 examples
Crissum: 10 examples
Vagina: 19 examples
Outside the vagina: 14 examples
Cervix uteri: 2 examples
1.3 wart body quantity:
The counting standard:
＜3: ten
＞3-10: Nian
＞10 or erythra fusion: thirty
Epimegetic: Their-registered
Except that 8 carriers, 89 condyloma acuminatum patient wart body＞thirty above persons are totally 30 people, occupy wart body patient's 31.25%
1.4 do not have clinical symptoms, but FQ-PCR-HPV detects positive person 8 people, male 3 people, woman 5 people, its original copy number: HPV6,11:4.53 * 108 2.61 * 106 4.96 * 106 6.72 * 104 1.6 * 102 3.77 * 102HPV 16,18:5.16 * 104 6.72 * 104
2 method of administration: divide secondary to take one pair of every day oral " the wart poison is clear ", prohibit before and after taking medicine and drink tea.
3 selected conditions: all participate in therapist all can not accept other type treatment, otherwise does not list among the observation.Treatment time was a standard with full 6 months, adhered to treatment in 6 months and the person of not healing, and it is invalid to be judged to.
4 contraindications: gestation or hemorrhage person taboo is arranged.
5 curative effect judging standards
Recovery from illness: whole wart bodies come off or FQ-PCR-HPV is 0 copy.
Invalid: minority wart body comes off or the FQ-PCR-HPV positive.
6 results
6.1 therapeutic effect: 97 philtrums
Cure: 95 people's cure rates: 97.93%
Invalid: 2 people account for 2.06%
31 patients through other treatment recurrence all cure.
6.2 the healing time analysis, among 95 healing persons:
≤ 1 month healing person: 24 people account for 25.26%
≤ 2 month healing persons: accumulative total 47 people account for 49.47%
≤ 3 month healing persons: accumulative total 61 people account for 64.21 ‰
≤ 4 month healing persons: accumulative total 81 people account for 85.26%
＜6 month healing persons: 91 people account for 95.79%
＞7 month healing persons: 4 people account for 4.21%
Average cure time is 2.74 months
6.38 the name carrier, the wherein cloudy commentaries on classics of 3 people FQ-PCR-HPV in 1 month, 2 people are cloudy the commentaries on classics in 2 months, and 3 people are cloudy the commentaries on classics in 4 months.
6.4 95 philtrums of curing have carried out the FQ-PCR-HPV detection behind 37 human therapies, account for healing person's 38.94%, they not only reach clinical cure but also the also all cloudy commentaries on classics of FQ-PCRHPV.The Dui of HPV surveyed Bi Inspection before and after wherein 24 people had done to treat, and accounted for whole healing persons' 25.26%
6.5 follow up a case by regular visits to and recur
Just entering follow-up period 6.5.195 remove 3 people among the name healing person, outside the less than 3 months, other patient's follow-up period accounts for 96.84% all more than 3 months; 91 people's follow-up period surpass 6 months, account for 96.8%, 83 people and follow up a case by regular visits to above 1 year, account for 88.29%, surpass 3 months conventional follow-up period.
6.5.2 recurrence: recur 2 people, relapse rate 2.1%.
7 discuss
7.1 in external pharmacodynamic experiment, contain in the test tube of HPV, add " the wart poison is clear ", promptly no longer can amplify the HPV copy after 24 hours, illustrate that " the wart poison is clear " is a kind of medicine that can selectively destroy HPV life basis DNA.This destruction is different with heating or chemical bactericide, and it is to have specificly, replaces HPV with HBS, and the wart poison can not destroy its DNA clearly.The moon that clinical 37 healing persons treat back FQ-PCR-HPV changes, the treatment mechanism that it also is described be by after the oral absorption in vivo kill virus obtain curative effect, this can explain that also it can obtain the reason of high curative rate and low relapse rate.
7.2 general follow-up period is 3 months.This group patient follow-up period surpasses 6 months persons and accounts for 96.8%, so its relapse rate is reliable.
7.3 clinical research shows." the wart poison is clear " has high cure rate (97.91%), is to calculate a course of treatment with 2 months, and the cure rate of a course of treatment is that the cure rate of 44.21%, two course of treatment is 85.26%.
Discover, surpass the patient who did not reach healing in 6 months, the treatment that holds on still can obtain to cure.
Though 7.4 the recurrent condyloma acuminatum patient shows it clinically to stubbornness on the conventional therapy and opposing, the wart poison still keeps good effect to them clearly.Each course cure rate of 30 selected recurrence patients does not have difference with the people that just falls ill, this group has a routine glans penis and the many condyloma acuminatum of coronary sulcus Mi cloth, once did 12 times freezing, at every turn all in postoperative 1 week recurrence, yet taking the wart poison promptly heals clear February, no longer recurrence does not show any treatment obstacle.
7.5 2 example recurrences are arranged among 95 patients that cure, the state of an illness of 2 examples is all not heavy, the quantity of wart body is at 1-3, all non-recurrence patient, and wart body time that comes off is also not long after controlling, 1 example is 1 month, in addition example is 4.5 months, and whether the something in common of 2 examples does not have the detection bodies inner virus to exist for the wart body does not carry out sufficient after treatment after coming off, therefore all had new wart body to occur after 2 months, in fact this belong to, and not cure be due to the drug withdrawal.
Be HPV 6,11 and HPV 16,18 7.6 cause the virus overwhelming majority of AC, experiment and clinical all proofs " the wart poison clearly " all have identical killing and the treatment ability to both.
7.7 clinical proof does not have the carrier and the subclinical patient of symptom, " the wart poison is clear " can remove its intravital HPV, not only stopped the generation of disease, and eliminated the source of infection, and significant on epidemiology, also provide the probability of treatment simultaneously to contacting close sex partner.
7.8 tumor and gynaecologist have confirmed that the chronic inapparent infection of the cervix uteri of HPV16 is the reason that causes cervical cancer, therefore " the wart poison is clear " can be considered as the cervix uteri carrier and remove the medication of HPV with the prevention cervical cancer.
Can cause epithelial change 7.9 infect HPV 16, bowenoid papulosis is exactly because infect the condyloma acuminatum with malignant change of cell that HPV 16 occurs.We once used " the wart poison is clear " to cure such patient, and in clinical symptoms and HPV disappearance, it is normal that the epithelial cell that cancerates on the pathology has also recovered.Illustrate that " the wart poison is clear " can make the cell reversal that cancerates because of HPV is normal cell.The early stage change of cervical cancer is divided into the CIN1-3 degree on its grade of malignancy pathology, and its pathological change is similar to bowenoid papulosis, therefore also can try out " the wart poison is clear " to observe its effect to the CIN that has HPV 16 to infect.
Embodiment 3
1. experiment medicine: make water decoction with following each prescription
2. experimental technique:, comprise external pharmacodynamic experiment and clinical investigation substantially with embodiment 1
3. experimental result: laboratory and clinical result are close substantially with prescription 1, but the most desirable with 1 effect of filling a prescription.
Claims (5)
1. the Chinese medicine of treatment human papilloma virus infection is made by following bulk drugs: Flos Carthami 6-60, Herba Equiseti Hiemalis 5-100.
2. the Chinese medicine of the described treatment human papilloma virus infection of claim 1 is made by following bulk drugs: Flos Carthami 10-60, Herba Equiseti Hiemalis 5-30.
3. the Chinese medicine of the described treatment human papilloma virus infection of claim 1 is made by following bulk drugs: Flos Carthami 10, Herba Equiseti Hiemalis 5.
4. the Chinese medicine of treatment human papilloma virus infection is made by following bulk drugs: Flos Carthami 6-60, Herba Equiseti Hiemalis 5-100, Rhizoma Cyperi 10-30.
5. the Chinese medicine of treatment human papilloma virus infection is made by following bulk drugs: Flos Carthami 6, Herba Equiseti Hiemalis 3, Rhizoma Cyperi 2.
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| CN111729027B (en) * | 2020-07-08 | 2021-11-26 | 上海市普陀区人民医院(上海纺织第一医院) | Traditional Chinese medicine composition for treating verruca plana and inhibiting HPV16 as well as preparation method and application thereof |
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