CN100571691C - A kind of antineoplastic patches for external use of bullatacin - Google Patents

Abstract

The invention discloses a kind of antineoplastic patches for external use of bullatacin, it comprises backing layer, drug-reservoir and adherent layer, selecting ventilative good cotton medical adhesive-bonded fabric for use is backing layer, drug-reservoir with the high-molecular gel acrylate pressure-sensitive adhesive as adhesive, containing deployed bullatacin medicinal liquid, is adherent layer with the polyester film through the silicone oil release treatment.It had both solved the shortcoming that antitumor drug is oral or the intravenously administrable toxic and side effects is big in the past, and it is big and have certain toxic shortcoming to skin irritation to have overcome traditional external use plaster again, and has reduced Financial cost.

Description

A kind of anti-tumor external patch of bratasine

technical field

The invention relates to an anti-tumor external drug preparation, in particular to an anti-tumor external patch.

Background technique

Annonaceae (Annonaceae) is a large plant group in tropical and subtropical regions, which contains alkaloids, terpenoids, flavonoids, annonaceae, polyoxycyclohexenes and styrylactones. Among them, the latter three types of compounds have anti-tumor activity, and have aroused widespread interest of scholars from various countries. Annonaceous acetogenins are a new class of natural products first discovered in Annonaceae in 1982. Annonaceolide has a wide range of physiological activities, the most typical of which are anti-tumor activity and cytotoxicity. Studies have shown that most annona lactones generally have a strong cytotoxic effect on tumor cells cultured in vitro.

At present, the incidence of tumors and cancers in the world is increasing year by year, and radiation, chemistry, drugs and other therapies must be used in the treatment process. Most anticancer drugs have poor selectivity for killing tumor cells, and radiotherapy and chemotherapy take a long time, have large doses, and are expensive. The anti-tumor drugs currently available on the market are mainly chemically synthesized, and their administration methods are mainly oral or intravenous administration, such as anti-tumor drugs 5-FU and vincristine. Among them, most of the anti-tumor drugs have mutagenic effects, and complete the inhibitory effect on tumors by blocking the replication of tumor DNA; they have toxic and side effects such as damage to white blood cells and liver cells, and have reactions such as nausea and hair loss.

In the present prior art, the pharmaceutical dosage form that CN1460473A proposes is injection or emulsion. However, in the implementation process, due to the problem of the production process, the dose of the drug cannot be controlled, and the clinical safety, effectiveness, and controllability cannot be guaranteed, so it is difficult to popularize and apply.

And traditional external patch mainly black plaster and rubber plaster. Black plasters contain a large amount of lead oxide, which is highly toxic; rubber plasters are highly irritating to the skin and have serious allergic reactions. In addition, the use of black plasters and rubber plasters will cause unfavorable aspects such as contamination of clothes, difficulty in removing the plasters, and uncomfortable skin, which directly affect the use of patients.

Contents of the invention

The technical problem to be solved by the present invention is to provide a kind of anti-tumor external patch of blatasine, which has not only solved the disadvantages of large toxic and side effects of oral or intravenous administration of anti-tumor drugs in the past, but also overcomes the harmful effects of traditional external patches on the skin. It has the disadvantages of high irritation and certain toxicity, and reduces the economic cost.

In order to solve the above problems, the present invention provides a bratasine anti-tumor external patch, which includes a backing layer, a drug reservoir and an anti-adhesive layer. The drug reservoir uses a polymer gel as an adhesive, containing Prepared burataxin liquid medicine.

The buratasine medicinal solution is obtained by dissolving the fine buratasine local medicine in a mixture of absolute ethanol and propylene glycol, stirring thoroughly, and mixing evenly.

The volume ratio of absolute ethanol and propylene glycol in the mixed solution is 1:1.

The weight ratio of the essence of the lataxine part medicine to the mixed solution is 1:1-1:10.

The polymer gel is an acrylate pressure sensitive adhesive.

The release layer is a polyester film treated with silicone oil release.

The preparation method of the external application patch of bratasine antitumor, it comprises the steps:

(1) Ingredients: Dissolve the essence of the part medicine containing buratasine in the mixed liquid of absolute ethanol and propylene glycol with a volume ratio of 1:1, and the weight ratio of the essence of the part medicine of buratasine to the mixture is 1: 1～1:10, fully stir to make it evenly mixed;

(2) Glue making: the pressure-sensitive adhesive is produced by adopting the production process of acrylate pressure-sensitive adhesive;

(3) Coating: Mix the mixed solution of buratacin topical medicine, absolute ethanol and propylene glycol with the pressure-sensitive adhesive after heating and melting, coat it on the anti-adhesive layer, and then cover the backing layer;

(4) Slicing: cutting into appropriate sizes (5×7cm, 7×10cm, 9×12cm, etc.); drying and cooling: to maximize the retention of active ingredients of the drug and enhance the efficacy; packaging: sealed with aluminum-plastic composite film .

Compared with prior art, the present invention has following advantage:

(1) The external patch of the present invention, which selects the new natural substance blatasine extracted from the custard apple plant as the main component, compared with the existing chemically synthesized antineoplastic drugs, the toxic and side effects are greatly reduced.

(2) The blatasine anti-tumor external patch of the present invention has little damage to normal cells, no nausea, hair loss, etc., while the existing anti-tumor drugs have obvious side effects such as leukocyte and liver cell damage, nausea, hair loss, etc. reaction.

(3) The present invention adopts an external patch, overcomes the shortcomings of oral or intravenous administration of existing antitumor drugs, and greatly reduces the toxic and side effects of the drugs.

(4) The present invention reduces the dosage of medicine and reduces the economic cost of treatment. For example, the dosage of the antineoplastic drug paclitaxel is 60mg, and the fine-quality medicine of buratasine of the present invention is only 30ug, which is 1/2000 of that of paclitaxel; Xin's 45-day treatment cost only 15,000 yuan.

(5) The present invention uses a new type of polymer gel as an adhesive, which has strong drug loading capacity, large drug inclusion capacity, high water content, good biocompatibility, strong affinity with the skin, and excellent air permeability and adhesion to the skin. It is superior to traditional black plaster and rubber plaster in terms of anti-irritation, irritation, and moisture retention. The patch made by this process has stronger air permeability, and the patient feels soft and comfortable after sticking, with suitable adhesion and no pain when peeling off. , and reduce allergies to a minimum.

(6) The curative effect of the present invention is rapid (it takes 30 minutes to 2 hours to take effect), the drug effect is long-lasting and stable, and the controllability is strong. If the administration needs to be interrupted, it is only necessary to remove the patch, which is very convenient. At the same time, it also has the advantages of long-lasting and stable drug effect and high drug bioavailability.

(7) The patch of the present invention does not use gasoline and other toxic and harmful organic solvents in production, which not only ensures the safety of drug production, reduces the physical harm to production workers, but also does not cause environmental pollution.

(8) The present invention uses polymer gel as the drug carrier, and the non-woven fabric is the external patch of the support of the gel drug, which diffuses to the patient's skin through the solvent, enters the dermis and subcutaneous tissue, passes through capillaries and lymphatic vessels The medicine is sent to the treatment site to achieve the purpose of treatment. The dosage is controlled by adjusting the administration area, and the drug is released continuously and stably. The allergic reaction of the drug to the liver and the gastrointestinal tract is avoided, the individual differences caused by the drug are reduced, and the use is more convenient and safe. Compared with injections, it greatly reduces the toxic and side effects of drugs injected into the human body.

Detailed ways

Embodiment 1: the antitumor external patch of blatasine of the present invention, it comprises backing layer, drug storage and anti-adhesive layer, selects the good cotton medical non-woven fabric of ventilation to be backing layer, and drug storage The polymer gel-acrylic pressure-sensitive adhesive is used as the adhesive agent, the prepared pratasine drug solution is contained, and the polyester film treated with silicone oil is used as the anti-adhesive layer.

Bratasine medicinal solution is to dissolve 198 grams of Bratasine partial drug essence in 1100ml mixture of absolute ethanol and propylene glycol with a volume ratio of 1:1, fully stir, mix evenly, and make an external patch 20400 patches (Size: 7×10cm).

Embodiment 2: the preparation method of the external-use patch of bratasine antitumor, it comprises the following steps: (1) batching: 198 grams of bratasine local medicinal essence are dissolved in the dehydrated alcohol that volume ratio is 1: 1 In the 1100ml mixed solution of propylene glycol, fully stir, make it mix evenly; (2) glue-making: adopt the production technology of acrylate pressure-sensitive adhesive to make pressure-sensitive adhesive; The mixture of high-quality goods, absolute ethanol and propylene glycol is mixed with the heated and melted pressure-sensitive adhesive, coated on the anti-adhesive layer, and then covered with the backing layer; (4) Slicing: cut into a suitable size (5×7cm , 7×10cm, 9×12cm and other specifications); dry and cool, sealed with aluminum-plastic composite film.

Embodiment 3: The beneficial effect of medicine described in the present invention is further set forth below by drug clinical trial:

Observational trials in the treatment of tumors:

According to research by domestic and foreign medical professionals, Bratasine not only has a strong anti-tumor effect, but also has the ability to reverse the multi-drug resistance of tumor cells. Utilizing the characteristic of blatasine, we used the extract of blatasine-containing medicine extracted from the seeds of custard apple to make an external patch to conduct a clinical observation test on tumor patients. Through the observation and treatment of 10 patients with different cancers in the past two months, it was found that the patch has greatly improved the pain of the patients, the concentration of tumor cells in the blood of some patients has decreased, and the respiratory and mental symptoms have improved significantly. It has been clinically proven that the patch has obvious curative effect and great application value in clinical treatment of tumors.

1. Selection of subjects

(1) According to the protocol of this experiment, priority is given to patients with primary lung cancer who have received radiotherapy and chemotherapy for more than 2 months and have no serious complications. Seven of the selected people in this trial had received radiotherapy and chemotherapy for more than 2 months, and the other 3 had not received radiotherapy and chemotherapy recently, and none of the 10 had particularly serious complications.

(2) There were 10 subjects in total, 8 males and 2 females, aged from 39 to 79 years old, with an average age of 62.8 years. The diagnoses of these 10 people were all confirmed by CT film, pathology or blood test.

2. Treatment plan

Usage and dosage: for external use, administer to the skin below the neck and extremities or follow the doctor's advice, 8 patches/time, 1 time/day, and the observation period is not less than 48 days.

3. Test results

Changes of clinical symptoms before and after treatment

4 Conclusion

1. Among the 10 patients observed, 2 had mild skin itching at the site of medication at the beginning, 1 could continue to use the drug after anti-allergic treatment, and the other 1 patient was relieved without treatment, and the rest showed no abnormalities. At present, no acute and chronic toxic and side effects related to this medicine have been found, so the safety of this medicine patch is certain.

2. Through small sample control, after using the drug, the patient's subjective symptoms and objective indicators have been improved to varying degrees. Therefore, through preliminary clinical application, the effect of the drug patch in treating tumors is affirmative.

Claims (3)

1. antineoplastic patches for external use of bullatacin, it comprises backing layer, drug-reservoir and adherent layer, it is characterized in that: drug-reservoir as adhesive, contains deployed bullatacin medicinal liquid with acrylate pressure-sensitive adhesive; Described bullatacin medicinal liquid is that bullatacin part YAOJING product are dissolved in the mixed liquor that volume ratio is 1: 1 dehydrated alcohol and propylene glycol, fully stir, mix homogeneously and getting, and the weight ratio of bullatacin part YAOJING product and mixed liquor is 1: 1～1: 10.

2. antineoplastic patches for external use of bullatacin according to claim 1 is characterized in that: adherent layer is the polyester film through the silicone oil release treatment.

3. the preparation method of antineoplastic patches for external use of bullatacin as claimed in claim 1, it comprises the steps:

(1) batching: will contain bullatacin part YAOJING product and be dissolved in the mixed liquor that volume ratio is 1: 1 dehydrated alcohol and propylene glycol, the weight ratio of bullatacin part YAOJING product and mixed liquor is 1: 1～1: 10, and abundant stirring makes its mix homogeneously;

(2) glue: adopt the production technology of acrylate pressure-sensitive adhesive to make pressure sensitive adhesive;

(3) coating: with the mixed liquor of bullatacin part YAOJING product, dehydrated alcohol and propylene glycol and the pressure sensitive adhesive mixing behind the heating and melting, coat on the adherent layer, cover again and go up backing layer;

(4) section, dry cooling and packing.