A traditional Chinese medicine composition for needle-free injection and its preparation method

Abstract

The present invention belongs to the technical field of pharmaceutical preparations, and discloses an extract of Vernonia anthelmintica for needleless injection and a preparation method thereof. A traditional Chinese medicine composition for needleless injection for treating vitiligo prepared by the method of the present invention can directly penetrate the skin surface and the stratum corneum of the skin after being injected by a needleless injection device, and deliver the extract of Vernonia anthelmintica and the extract of Psoralea corylifolia into the skin to exert the medicinal effect, and is applicable to the treatment of vitiligo. A traditional Chinese medicine composition for needleless injection for treating vitiligo prepared by the method of the present invention can protect the drug from staying inside the skin for a long time, exert the medicinal effect for a long time, and avoid the disadvantage of rapid clearance of traditional skin ointments. At the same time, this treatment method solves the problem that the current clinical treatment of vitiligo requires the use of an ultraviolet irradiation instrument. The characteristics of the administration method determine that a traditional Chinese medicine composition for needleless injection for treating vitiligo is safe and convenient for daily use, the patient has no pain, and the acceptance degree of the treatment is high.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical preparations, and particularly relates to a needle-free injectable traditional Chinese medicine composition for treating vitiligo and a preparation method thereof. Background Art

[0002] Vitiligo is a common depigmenting skin disease, with an estimated prevalence of 0.5 - 2% in the global population. This disease is characterized by the selective loss of melanocytes, resulting in typical scaleless, chalky white macules. In recent years, researchers have made considerable progress in understanding the pathogenesis of vitiligo, and it has now been clearly classified as an autoimmune disease. In real life, although vitiligo causes great psychological distress to patients, it is usually regarded as a cosmetic problem and has not received due attention.

[0003] Currently, the treatment of vitiligo mostly uses narrow-band UV-B light irradiation, or UV-B light irradiation can be combined with other treatment methods to promote pigmentation. Although the above various methods are safe and effective in application, due to the limitations of the treatment methods, patients need to receive professional treatment under the guidance of corresponding technical personnel, which undoubtedly requires patients to adhere to it for a long time and will also cause great economic pressure on patients. Therefore, the development of a more convenient, inexpensive alternative treatment method is imminent. Summary of the Invention

[0004] Aiming at the defects of the above prior art, the technical problem solved by the present invention is to provide a needle-free injectable traditional Chinese medicine composition for treating vitiligo, and also to provide a preparation method of a needle-free injectable traditional Chinese medicine composition for treating vitiligo.

[0005] To solve the technical problems of the present invention, the technical problem solved by the present invention is to provide a needle-free injectable traditional Chinese medicine composition for treating vitiligo, which is characterized in that:

[0006] The needle-free injectable traditional Chinese medicine composition for treating vitiligo is in liquid form, and the needle-free injectable traditional Chinese medicine composition for treating vitiligo includes an active substance, a modified component and a solvent component;

[0007] Furthermore, the active substance is selected from one or more of Vernonia anthelmintica extract and Psoralea corylifolia extract;

[0008] The modified component is selected from one or more of co-solvent enhancer, stabilizer, retention component and other components;

[0009] The solvent component is selected from one or more of water for injection, phosphate buffer solution, physiological saline and glucose solution.

[0010] Furthermore, the co-solvent is selected from one or more of dimethyl sulfoxide, glycerol, castor oil, ethanol, polysorbate, polyvinyl pyrrolidone, and polyethylene glycol;

[0011] The stabilizer is selected from one or more of chitosan, sodium hyaluronate, polyurethane, carrageenan, gelatin, and bletilla striata polysaccharide;

[0012] The retention component is selected from one or more of polyethylene glycol, egg yolk phosphatidylcholine, soybean phosphatidylcholine, cholesterol, distearoyl phosphatidylethanolamine, and dopamine;

[0013] The other components are one or more of a pH regulator and an osmotic pressure regulator, the pH regulator is selected from one or more of sodium hydroxide, hydrochloric acid, phosphoric acid, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, citric acid, sodium citrate, and citric acid, and the osmotic pressure regulator is selected from one or more of sodium chloride, calcium chloride, potassium chloride, and sucrose.

[0014] The Chinese medicine composition for needle-free injection for treating vitiligo is also characterized in that:

[0015] The active substance accounts for 0.5-2 parts by weight, and the mass ratio of the Vernonia extract to the Psoralea corylifolia extract is 0.5-2;

[0016] The auxiliary latent solvent accounts for 0.05-1.5 parts by mass, the stabilizer accounts for 0.01-1 parts by mass, and the retention component accounts for 0.1-8 parts by mass;

[0017] The pH regulator accounts for 0-1.5 parts by mass, and the osmotic pressure regulator accounts for 0-1 parts by mass;

[0018] The solvent accounts for 20-60 parts by mass.

[0019] The method for preparing the Chinese medicine composition for needle-free injection for treating vitiligo is characterized in that:

[0020] The preparation method of the Chinese medicine composition for needle-free injection for treating vitiligo comprises the following steps:

[0021] ① Adding a co-solvent and a stabilizer to a part of the solvent and fully dissolving them to obtain solution A;

[0022] ② Dissolve the retained component in another part of the solvent and mix thoroughly to obtain solution B;

[0023] ③ dissolving the Vernonia extract and the Psoralea corylifolia extract in solution B according to a certain preparation method to obtain solution C, wherein the preparation method can be direct dissolution, shear-assisted dissolution, stirring-assisted dissolution, ultrasonic homogenization, or emulsification;

[0024] ④ Slowly add the above solution A to solution C. During the addition process, both are maintained at a water bath temperature of 50 - 60°C, and under the shearing condition of 3000 - 5000 rpm. After the addition is completed, solution D is obtained.

[0025] ⑤ Adjust the pH and osmotic pressure of the above solution D. Adjust the pH to 6.7 - 7.0 and the osmotic pressure to 280 - 320 mOsm / kg.

[0026] ⑥ The needle - free injection traditional Chinese medicine composition for treating vitiligo with adjusted pH and osmotic pressure is obtained after aseptic treatment and sub - packaging.

[0027] Among them, the aseptic treatment can select the membrane filtration method, autoclaving method, or aseptic filling method according to specific conditions.

[0028] Among them, the partial solvent is 10% - 70% of the total solvent volume.

[0029] The usage method of the needle - free injection traditional Chinese medicine composition for treating vitiligo is characterized in that

[0030] The needle - free injection traditional Chinese medicine composition for treating vitiligo is filled into a national standard container for needle - free drug delivery and used in combination with a needle - free syringe; according to needs, the daily administration frequency can be adjusted, and the maximum daily administration does not exceed 3 times.

[0031] The usage method of the needle - free injection traditional Chinese medicine composition for treating vitiligo is further characterized in that

[0032] The application of the needle - free injection traditional Chinese medicine composition in the preparation of drugs for treating and / or preventing vitiligo.

[0033] The beneficial effects of the present invention are as follows:

[0034] A needle - free injection traditional Chinese medicine composition for treating vitiligo prepared by the method of the present invention is applicable to the treatment of vitiligo. This treatment method solves the current problem in clinical treatment of vitiligo that requires the use of ultraviolet irradiation instruments. The characteristics of the administration method determine that the needle - free injection traditional Chinese medicine composition for treating vitiligo is safe, convenient, painless for patients in daily use, and has a high acceptance rate for treatment.

[0035] A needle - free injection traditional Chinese medicine composition for treating vitiligo prepared by the method of the present invention can protect the drug from staying inside the skin for a long time after preparation, exert its efficacy for a long time, and avoid the disadvantage of rapid clearance of traditional skin ointments. Brief Description of the Drawings

[0036] Figure 1 Safety evaluation of the needle - free injection traditional Chinese medicine composition for treating vitiligo prepared in Example 2 on the skin;

[0037] Figure 2 Liquid phase spectrum of Vernonia extract and Psoralea corylifolia extract;

[0038] Figure 3 A comparison of the skin absorption of the Chinese medicine composition for needle-free injection for treating vitiligo prepared in Example 4 with other administration methods;

[0039] Figure 4 A comparison of the therapeutic effect of the Chinese medicine composition for needle-free injection for treating vitiligo prepared in Example 5 with other administration methods in treating vitiligo. DETAILED DESCRIPTION

[0040] The present invention is further described in detail below by way of examples, which are intended to illustrate the present invention rather than to limit the present invention. Furthermore, it should be particularly noted that, for those skilled in the art, several improvements and modifications may be made to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the scope of protection of the present invention.

[0041] Example 1: Preparation of a Chinese medicine composition for needle-free injection for treating vitiligo

[0042] 1. Prescription (1000mL)

[0043]

[0044] 2. Add polysorbate, sodium hyaluronate and bletilla striata polysaccharide into 500 mL of solvent and fully dissolve them to obtain solution A;

[0045] 3. Dissolve dopamine in another 500 mL of solvent and mix thoroughly to obtain solution B;

[0046] 4. Dissolve 10 g of Vernonia extract in solution B by a shear-assisted dissolution method to obtain solution C;

[0047] 5. Slowly add the above solution A to solution C. During the addition process, both keep the water bath temperature at 55-57°C and shear at 3500rpm. After the addition is completed, solution D is obtained;

[0048] 6. Adjust the pH and osmotic pressure of the above solution D to 6.7-7.0 and 280-320 mOsm / kg;

[0049] 7. The needle-free injection Chinese medicine composition for treating vitiligo with adjusted pH and osmotic pressure is aseptically treated and packaged;

[0050] During use, the patient uses a needle-free injection device to directly inject the Chinese medicine composition for needle-free injection of vitiligo into the local affected area of ​​vitiligo.

[0051] Example 2: Preparation of a needleless injection traditional Chinese medicine composition for treating vitiligo

[0052] 1. Prescription (1000 mL)

[0053]

[0054] 2. Add dimethyl sulfoxide, sodium hyaluronate, and chitosan to 800 mL of solvent and dissolve them thoroughly to obtain Solution A;

[0055] 3. Dissolve distearoyl phosphatidylethanolamine in another 200 mL of solvent and mix well to obtain Solution B;

[0056] 4. Dissolve 13 g of psoralen extract by direct dissolution method in Solution B to obtain Solution C;

[0057] 5. Slowly add the above Solution A to Solution C. During the addition process, keep the water bath temperature of both at 50 - 55 °C, and under the shearing condition of 5000 rpm, obtain Solution D after the addition;

[0058] 6. Adjust the pH and osmotic pressure of the above Solution D. Adjust the pH to 6.7 - 7.0 and the osmotic pressure to 280 - 320 mOsm / kg;

[0059] 7. The needleless injection traditional Chinese medicine composition for treating vitiligo with adjusted pH and osmotic pressure is obtained after aseptic treatment and subpackaging;

[0060] During use, the patient directly injects the needleless injection traditional Chinese medicine composition for treating vitiligo into the local affected area of vitiligo with the help of a needleless injection device.

[0061] Example 3: Preparation of a needleless injection traditional Chinese medicine composition for treating vitiligo

[0062] 1. Prescription (1000 mL)

[0063]

[0064] 2. Add glycerol and gelatin to 400 mL of sucrose solution and dissolve them thoroughly to obtain Solution A;

[0065] 3. Dissolve egg yolk lecithin, cholesterol, and distearoyl phosphatidylethanolamine in 600 mL of injection water and mix well to obtain Solution B;

[0066] 4. Dissolve 8 g of vernonia anthelmintica extract and 8 g of psoralen extract in Solution B by ultrasonic homogenization method to obtain Solution C;

[0067] 5. Slowly add the above solution A to solution C. During the addition process, both keep the water bath temperature at 55-60°C and under the shear condition of 4500rpm. After the addition is completed, solution D is obtained;

[0068] 6. Adjust the pH and osmotic pressure of the above solution D to 6.7-7.0 and 280-320 mOsm / kg;

[0069] 7. The needle-free injection Chinese medicine composition for treating vitiligo with adjusted pH and osmotic pressure is aseptically treated and packaged;

[0070] During use, the patient uses a needle-free injection device to directly inject the Chinese medicine composition for needle-free injection of vitiligo into the local affected area of ​​vitiligo.

[0071] Example 4: Preparation of a Chinese medicine composition for needle-free injection for treating vitiligo

[0072] 1. Prescription (1000mL)

[0073]

[0074] 2. Add polyvinyl pyrrolidone, bletilla striata polysaccharide and sodium hyaluronate to 500 mL of sucrose solution and fully dissolve them to obtain solution A;

[0075] 3. Dissolve polyethylene glycol and soybean lecithin in 500 mL of phosphate buffer and mix thoroughly to obtain solution B;

[0076] 4. Dissolve 5 g of Vernonia extract and 10 g of Psoralea corylifolia extract in solution B by emulsification to obtain solution C;

[0077] 5. Slowly add the above solution A to solution C. During the addition process, both keep the water bath temperature at 58-60°C and under the shear condition of 4000rpm. After the addition is completed, solution D is obtained;

[0078] 6. Adjust the pH and osmotic pressure of the above solution D to 6.7-7.0 and 280-320 mOsm / kg;

[0079] 7. The needle-free injection Chinese medicine composition for treating vitiligo with adjusted pH and osmotic pressure is aseptically treated and packaged;

[0080] During use, the patient uses a needle-free injection device to directly inject the Chinese medicine composition for needle-free injection of vitiligo into the local affected area of ​​vitiligo.

[0081] Example 5: Preparation of a Chinese medicine composition for needle-free injection for treating vitiligo

[0082] 1. Prescription (1000mL)

[0083]

[0084] 2. Add polyethylene glycol, polyurethane, and carrageenan to 700 mL of injection and dissolve thoroughly to obtain Solution A;

[0085] 3. Dissolve distearoyl phosphatidylethanolamine in another 300 mL of water for injection and mix thoroughly to obtain Solution B;

[0086] 4. Dissolve 12 g of Vernonia anthelmintica extract and 6 g of Psoralea corylifolia extract in Solution B by ultrasonic homogenization to obtain Solution C;

[0087] 5. Slowly add the above Solution A to Solution C. During the addition process, both are maintained at a water bath temperature of 50 - 55 °C, and under the shearing condition of 3000 rpm. After the addition is completed, obtain Solution D;

[0088] 6. Adjust the pH and osmotic pressure of the above Solution D. Adjust the pH to 6.7 - 7.0 and the osmotic pressure to 280 - 320 mOsm / kg;

[0089] 7. The needle - free injection traditional Chinese medicine composition for treating vitiligo with adjusted pH and osmotic pressure is obtained after aseptic treatment and filling;

[0090] During use, the patient directly injects the needle - free injection traditional Chinese medicine composition for treating vitiligo into the local affected area of vitiligo through a needle - free injection device.

[0091] Experimental Example 1: Study on the skin penetration ability and subcutaneous diffusion ability of the needle - free injection traditional Chinese medicine composition for treating vitiligo of the present invention

[0092] Use the abdominal skin of SD rats to evaluate the skin penetration ability and subcutaneous diffusion ability of the needle - free injection traditional Chinese medicine composition for treating vitiligo. The sample of the needle - free injection traditional Chinese medicine composition for treating vitiligo used in this experimental example is the needle - free injection traditional Chinese medicine composition for treating vitiligo prepared in Example 3, and the needle - free injection device used is a needle - free injection device already on the market of an enterprise in Beijing. First, remove the abdominal skin of SD rats, depilate, and fix it on a foam board. Press the needle - free injection traditional Chinese medicine composition of the present invention tightly against the skin through the needle - free injection device and inject it into the rat skin. Subsequently, remove the needle - free injection device, use filter paper to absorb the residual liquid on the surface of the rat skin, and observe the injection needle hole with the help of a magnifying glass. Then, take the rat skin at the injection site with a 0.6 cm corneal trephine, and after tissue treatment, perform content analysis with the help of a high - performance liquid chromatograph.

[0093] The results showed that after the needleless injection traditional Chinese medicine composition for treating vitiligo in Example 3 of the present invention was injected into the skin, no residual liquid was found on the skin surface of the rats. The results observed with the aid of a magnifying glass showed that there was only a tiny wound on the skin of the rats, and the wound was much smaller than the skin wound caused by the needle of a 1 mL syringe. This indicated that the needleless injection traditional Chinese medicine composition for treating vitiligo under this method was all injected into the body, promoting the transdermal delivery of the drug.

[0094] Experimental Example 2: Study on the individual safety and tissue irritation of a needleless injection traditional Chinese medicine composition for treating vitiligo of the present invention

[0095] The sample of the needleless injection traditional Chinese medicine composition for treating vitiligo used in this experimental example was the needleless injection traditional Chinese medicine composition for treating vitiligo prepared in Example 2, and the needleless injection device used was a needleless injection device already on the market of an enterprise in Beijing. Male SD rats (weighing 200 - 250 g) were grouped according to the random number table method. After administration, the survival status of the rats and the pathological status of the rats and their tissues were observed.

[0096] The results showed that none of the SD rats in each group died after administration, indicating that the needleless injection traditional Chinese medicine composition for treating vitiligo in Example 2 of the present invention had good safety. The histopathological results showed that after administration of the needleless injection Vernonia anthelmintica extract in Example 2 of the present invention, no obvious lymphocyte infiltration was seen, and no tissue damage or necrosis was seen, which also indicated that the needleless injection Vernonia anthelmintica extract of the present invention had good safety. Experimental Example 3: Study on the drug distribution of a needleless injection traditional Chinese medicine composition for treating vitiligo of the present invention in the skin

[0097] The sample of the needleless injection traditional Chinese medicine composition for treating vitiligo used in this experimental example was the needleless injection traditional Chinese medicine composition for treating vitiligo prepared in Example 4, and the needleless injection device used was a needleless injection device already on the market of an enterprise in Beijing. Male SD rats (weighing 200 - 250 g) were grouped according to the random number table method: (1) the needle injection administration group, (2) the needleless injection administration group, and (3) the skin smear group. There were 30 rats in each group. The rats were administered with the drugs in the following grouping settings respectively. After administration, they were raised for 4 h, and then the skin tissues of the rats were taken. The contents of Vernonia anthelmintica extract and Psoralea corylifolia extract in the skin were determined by high performance liquid chromatography. The high performance liquid chromatography spectrogram was as Figure 2 shown.

[0098] The results were as Figure 3 shown: Higher contents of Vernonia anthelmintica extract and Psoralea corylifolia extract could be detected in the skin of the needle injection group and the needleless injection group, both of which were higher than those in the skin smear administration group, and the drug content in the needleless injection group was higher.

[0099] Experimental Example 4: Pharmacodynamic Study of a Needle-Free Injectable Traditional Chinese Medicine Composition for the Treatment of Vitiligo according to the Present Invention

[0100] The sample of the needle-free injectable traditional Chinese medicine composition for the treatment of vitiligo used in this experimental example was the needle-free injectable traditional Chinese medicine composition for the treatment of vitiligo prepared in Example 5, and the needle-free injection device used was a needle-free injection device already on the market of an enterprise in Beijing. All volunteers in this experimental example were recruited voluntarily, fully read and understood the informed consent form, and the experimental process met the ethical welfare requirements. After all volunteers were taught the usage method, they administered the medicine by themselves. After continuous administration for one month, the drug effect was traced. The results showed that the patients in the needle-free administration group rarely reported that the administration method was different from that of the needle injection, and the skin changes at the vitiligo affected area showed that the needle-free administration group had a better treatment effect, such as Figure 4 .

Claims

1. A traditional Chinese medicine composition for needle-free injection, characterized in that the traditional Chinese medicine composition for needle-free injection is in liquid form and comprises an active substance, a modified component and a solvent component; the active substance is Vernonia anthelmintica extract and Psoralea corylifolia extract; the modified component is a co-solvent enhancer, a stabilizer, a retention component and other components; the solvent component is selected from one or more of water for injection, phosphate buffer solution, normal saline and glucose solution; the other components are one or more of a pH regulator and an osmotic pressure regulator; the active substance accounts for 0.5-2 parts by mass, and the mass ratio of Vernonia anthelmintica extract to Psoralea corylifolia extract is 1:0.5-1:2; the co-solvent enhancer accounts for 0.05-1.5 parts by mass, the stabilizer accounts for 0.01-1 part by mass, and the retention component accounts for 0.1-8 parts by mass; the pH regulator accounts for 0-1.5 parts by mass, and the osmotic pressure regulator accounts for 0-1 part by mass; the solvent accounts for 20-60 parts by mass; the co-solvent enhancer is selected from one or more of dimethyl sulfoxide, glycerol, castor oil, ethanol, polysorbate, polyvinylpyrrolidone, polyethylene glycol; the stabilizer is selected from one or more of chitosan, sodium hyaluronate, polyurethane, carrageenan, gelatin, and Bletilla striata polysaccharide; the retention component is selected from one or more of polyethylene glycol, egg yolk lecithin, soybean lecithin, cholesterol, distearoyl phosphatidylethanolamine, and dopamine; the pH regulator is selected from one or more of sodium hydroxide, hydrochloric acid, phosphoric acid, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, citric acid, sodium citrate, and citric acid, and the osmotic pressure regulator is selected from one or more of sodium chloride, calcium chloride, potassium chloride, and sucrose.

2. A preparation method of the traditional Chinese medicine composition for needle-free injection according to claim 1, characterized in that the preparation method of the traditional Chinese medicine composition for needle-free injection comprises the following steps: ① Add a co-solvent enhancer and a stabilizer to a part of the solvent and dissolve them fully to obtain solution A; ② Dissolve the retention component in another part of the solvent and mix well to obtain solution B; ③ Dissolve the Vernonia anthelmintica extract and the Psoralea corylifolia extract in solution B according to a certain preparation method to obtain solution C, wherein the preparation method can be direct dissolution, shear-assisted dissolution, stirring-assisted dissolution, ultrasonic homogenization method, or emulsification method; ④ Slowly add the above solution A to solution C, and keep the water bath temperature of both at 50-60 °C during the addition process, and under the shearing condition of 3000-5000 rpm, and obtain solution D after the addition is completed; ⑤ Adjust the pH and osmotic pressure of the above solution D, adjust the pH to 6.7-7.0, and adjust the osmotic pressure to 280-320 mOsm / kg; ⑥ The traditional Chinese medicine composition for needle-free injection with the adjusted pH and osmotic pressure is obtained after aseptic treatment and sub-packaging; wherein, the aseptic treatment can be selected from membrane filtration method, autoclaving method, and aseptic filling method according to specific conditions.

3. According to the preparation method of the traditional Chinese medicine composition for needle-free injection described in claim 2, characterized in that the part of the solvent is 10%-70% of the total solvent volume.

4. Use of the traditional Chinese medicine composition for needleless injection according to claim 1 in the preparation of a medicament for treating and / or preventing vitiligo; Among them, The needleless injection traditional Chinese medicine composition for treating vitiligo is filled into a national standard container for needleless administration and used in conjunction with a needleless syringe; the number of daily administrations can be adjusted according to requirements, and the maximum number of daily administrations does not exceed 3 times.

Images