CN117357480B

CN117357480B - Composition for needleless percutaneous injection

Info

Publication number: CN117357480B
Application number: CN202311681459.8A
Authority: CN
Inventors: 檀华进; 杨玉莹; 王登才; 毕珊珊; 刘成林; 张春辉; 罗四海; 杨玲
Original assignee: Beijing Zhongkelihua Pharmaceutical Research Institute Co ltd
Current assignee: Beijing Zhongkelihua Pharmaceutical Research Institute Co ltd
Priority date: 2023-12-08
Filing date: 2023-12-08
Publication date: 2024-03-29
Anticipated expiration: 2043-12-08
Also published as: CN117357480A

Abstract

The present embodiments provide compositions for needleless transdermal injection, including scar inhibitors, specific targets, phospholipid diselenide polyethylene glycol, phospholipids, cholesterol, and neutral fat. According to the needleless percutaneous injection composition, a response type cell membrane is obtained by mixing a hyperplastic scar fiber cell membrane, a keloid fiber cell membrane and a phospholipid diselenide bond polyethylene glycol, and after targeting and positioning to an affected part, active ingredients are released in a manner of combining burst release and sustained release by the mutual coordination of the phospholipid diselenide bond polyethylene glycol and a liposome, so that the blood concentration is quickly reached, long-acting treatment is maintained, the injection frequency during treatment is reduced, and the damage to skin during injection is reduced; and the fear of the needle injection to the patient can be reduced, and the compliance of the patient is improved.

Description

Composition for needleless percutaneous injection

Technical Field

The present application relates to the field of medicine, and in particular to a composition for needleless percutaneous injection.

Background

Scar is a collective term for a series of morphological and histopathological changes in human skin after it has been subjected to a wound. The scar not only seriously affects the appearance and the image of the patient, but also greatly reduces the life quality of the patient and brings psychological and economic burden to the patient, so that the scar prevention and treatment and the medical research thereof have important social and economic values.

Currently, the most common pharmaceutical treatment for scars is glucocorticoid. Namely, the glucocorticoid medicine is injected to the affected part through an injection needle.

However, scar treatment is a lengthy procedure, and frequent injections through the needle not only result in poor patient compliance, but also can cause damage to the skin and even exacerbate the scar severity.

Disclosure of Invention

In view of the above, the present application provides a composition for needle-free transdermal injection to at least partially solve the above-mentioned problems.

In order to achieve the above purpose, the present application is realized by the following technical scheme:

in a first aspect, a composition for needleless transdermal injection of the present application comprises:

scar inhibitor, specific targeting, phospholipid diselenide polyethylene glycol, phospholipid, cholesterol and neutral fat;

the ratio of the mass of scar inhibitor to the total mass of specific target, phospholipid, cholesterol and neutral fat is 1:15-24;

the mass ratio of the phospholipid diselenide polyethylene glycol to the specific targeting agent is 1:7-15;

the ratio of the total mass of the phospholipid, the cholesterol and the neutral fat to the mass of the specific targeting agent is 1:0.1-1;

the mass ratio of the phospholipid to the neutral fat is 1:2.5-7.5;

the mass ratio of the phospholipid to the cholesterol is 1:1.25-3;

the concentration of scar inhibitor in the composition for needleless percutaneous injection is 0.25-1mg/ml.

For the mass of scar inhibitor, the ratio of the mass to the total mass of specific targeting, phospholipids, cholesterol and neutral fat, 1:15-24 refers to any value in the range of 1:15 to 1:24, such as 1:15, 1:15.5, 1:16, 1:16.5, 1:17, 1:17.5, 1:18, 1:18.5, 1:19, 1:19.5, 1:20, 1:20.5, 1:21, 1:21.5, 1:22, 1:22.5, 1:23, 1:23.5 and 1:24.

For mass ratio of phospholipid diselenide polyethylene glycol to specific target, 1:7-15 refers to any value in the range of 1:7 to 1:15, e.g., 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5, 1:10, 1:10.5, 1:11, 1:11.5, 1:12, 1:12.5, 1:13, 1:13.5, 1:14, 1:14.5, and 1:15.

For the ratio of the total mass of phospholipids, cholesterol and neutral fat to the mass of specific targeting, 1:0.1-1 refers to any value in the range of 1:0.1 to 1:1, such as 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9 and 1:1.

For a mass ratio of phospholipids to neutral fat, 1:2.5-7.5 refers to any value in the range of 1:2.5 to 1:7.5, such as 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5 and 1:7.

For the mass ratio of phospholipids to cholesterol, 1:1.25-3 refers to any value in the range of 1:1.25 to 1:3, such as 1:1.25, 1:1.4, 1:1.5, 1:1.6, 1:1.8, 1:2, 1:2.1, 1:2.2, 1:2.4, 1:2.6, 1:2.7, 1:2.8, 1:2.9, and 1:3.

For the concentration of scar inhibitor, 0.25-1mg/ml refers to any value in the range of 0.25mg/ml to 1mg/ml, such as 0.25mg/ml, 0.3mg/ml, 0.35mg/ml, 0.4mg/ml, 0.45mg/ml, 0.5mg/ml, 0.55mg/ml, 0.6mg/ml, 0.65mg/ml, 0.7mg/ml, 0.75mg/ml, 0.8mg/ml, 0.85mg/ml, 0.9mg/ml, 0.95mg/ml, and 1mg/ml.

Preferably, the specific targets comprise: a proliferative scar fibroblast membrane and/or a keloid fibroblast membrane.

When the specific target comprises a hypertrophic scar fibrous cell membrane and a keloid fibrous cell membrane, the mass ratio of the hypertrophic scar fibrous cell membrane to the keloid fibrous cell membrane is 1:1.

In particular, the specific target may be a single substance, such as a hypertrophic scar fibroblast membrane, or a keloid fibroblast membrane. The specific target may also be a composition, such as a composition of a hypertrophic scar fibroblast membrane and a keloid fibroblast membrane.

When the specific target is a composition consisting of a hypertrophic scar fibroblast and a keloid fibroblast, the mass ratio of the hypertrophic scar fibroblast to the keloid fibroblast is 1:1.

It should be noted that the hypertrophic scar fibroblast membrane refers to the cell membrane of the hypertrophic scar fibroblast. Similarly, keloid fibroblast membrane refers to the cell membrane of keloid fibroblasts.

Preferably, the scar inhibitor comprises: triamcinolone acetonide or betamethasone.

Preferably, the phospholipid comprises: electronegative phospholipids and ampholytic phospholipids;

the mass ratio of electronegative phospholipids to ampholytic phospholipids is 1:0.25-0.5.

For mass ratios of electronegative phospholipids to ampholytic phospholipids, 1:0.25-0.5 refers to any value in the range of 1:0.25 to 1:0.5, such as 1:0.25, 1:0.27, 1:0.29, 1:0.3, 1:0.32, 1:0.34, 1:0.35, 1:0.36, 1:0.38, 1:0.4, 1:0.42, 1:0.44, 1:0.45, 1:0.46, 1:0.48, 1:0.49, and 1:0.5.

Preferably, when the electronegative phospholipid is distearoyl phosphatidylethanolamine and the ampholytic phospholipid is soybean lecithin, the neutral fat comprises glycerol trioleate.

Electronegative phospholipid means a negatively charged phospholipid. Ampholytic phospholipids refer to phospholipids comprising two hydrophilic and hydrophobic moieties that differ in nature.

Preferably, the mass ratio of the phospholipid diselenide polyethylene glycol to the specific targeting agent is 1:10.

The preparation method of the composition for needleless percutaneous injection comprises the following steps:

dissolving cholesterol, phospholipid and neutral fat in organic solvent to obtain oil phase.

Specifically, the organic solvent for dissolving cholesterol, phospholipids and neutral fat may be chloroform, diethyl ether, or a mixture of chloroform and diethyl ether, but is not limited thereto.

Dissolving the active ingredients, and mixing with the oil phase to obtain colostrum.

Specifically, when the active ingredient is triamcinolone acetonide, the triamcinolone acetonide can be added into the oil phase and uniformly mixed to obtain colostrum; when the active ingredient is betamethasone, the betamethasone and the sodium chloride solution or the glucose solution or the combination of the two can be mixed evenly. And adding the betamethasone water solution into the oil phase, and uniformly mixing to obtain the colostrum. The osmotic pressure of the sodium chloride solution and the glucose solution for dissolving the betamethasone is 275-285mmol/L. The osmotic pressure of the sodium chloride solution and the glucose solution is any value in the range of 275-285mmol/L, such as 275mmol/L, 280mmol/L, and 285mmol/L.

Adding colostrum into injectable water, and stirring to obtain multiple emulsion. And carrying out vacuum drying treatment on the compound emulsion to obtain liposome solid.

Adding water for injection into liposome solid to obtain liposome solution.

Obtain the proliferation scar fibroblast membrane and keloid fibroblast membrane, and obtain the specific target.

Specifically, the hypertrophic scar fibroblast and keloid fibroblast may be obtained by centrifuging hypertrophic scar fibroblast and keloid fibroblast, dispersing the centrifuged hypertrophic scar fibroblast and keloid fibroblast into phosphate buffer salt solution (pH 7.4) containing 0.1% protein inhibitor, and ultrasonic crushing the heavy suspension. Sequentially performing centrifugation to obtain cell membranes. Sequentially re-suspending the cell membrane in phosphate buffer salt solution to obtain hypertrophic scar fibroblast membrane and keloid fibroblast membrane. Wherein the phosphate buffer solution at the time of resuspension does not contain protease inhibitor of ethylenediamine tetraacetic acid.

Mixing the specific target with phospholipid diselenide polyethylene glycol, and homogenizing to obtain a mixture.

Specifically, the specific targeting substance and the polyethylene glycol with the phospholipid diselenide bond are homogenized, so that a mixture with uniform particles and smaller particle size can be obtained.

Adding the mixture into liposome solution, incubating, sequentially centrifuging, and re-dispersing the centrifuged precipitate to obtain the composition for needleless percutaneous injection.

Specifically, the precipitate after centrifugation may be redispersed by adding the centrifuged material to water for injection to clean the unencapsulated portion and achieve redispersion.

Specifically, the centrifugation time is 5-8min, for example, 5min, 6min, 7min, and 8min.

From the above technical solutions, the present application provides a composition for needle-free percutaneous injection. The composition for needleless percutaneous injection comprises: triamcinolone acetonide/betamethasone, hypertrophic scar fibre cell membranes and keloid fibre cell membranes, phospholipid diselenide polyethylene glycol, distearoyl phosphatidylethanolamine, soybean lecithin, cholesterol, triolein and water for injection. The responsive cell membrane can be obtained by mixing the hypertrophic scar fiber cell membrane, the keloid fiber cell membrane and the phospholipid diselenide polyethylene glycol, and the active ingredients are released in a manner of combining burst release and sustained release by the mutual coordination of the phospholipid diselenide polyethylene glycol and the liposome after targeting and positioning to the affected part, so that the blood concentration is quickly reached, and meanwhile, long-acting treatment is kept, the injection frequency during treatment is reduced, and the damage to skin during injection is lightened; and the fear of the needle injection to the patient can be reduced, and the compliance of the patient is improved.

Drawings

In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are some embodiments of the present application, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.

FIG. 1 is a graph of quality inspection results for each prescription provided in example 2 of the present application;

FIG. 2 is a graph showing the results of examining the amounts and types of phospholipids provided in example 3 of the present application;

FIG. 3 is a graph showing the results of examining the amount of cholesterol used in example 4 of the present application;

FIG. 4 is a view showing the results of examining the type and amount of neutral fat as provided in example 5 of the present application;

FIG. 5 is a plot of the amount of specific targeting provided in example 6 of the present application;

FIG. 6 is a graph showing the results of examining the amount of polyethylene glycol having a phospholipid diselenide bond in example 7 of the present application;

FIG. 7 is the results of an in vitro hemolysis assay provided in example 8 of the present application;

FIG. 8 is the results of an in vitro release test provided in example 9 of the present application;

fig. 9 is the results of the anti-rabbit ear scar test provided in example 10 of the present application.

Description of the embodiments

In order to better understand the technical solutions in the embodiments of the present application, the following description will clearly and completely describe the technical solutions in the embodiments of the present application with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are only some embodiments of the present application, but not all embodiments. All other embodiments obtained by a person of ordinary skill in the art based on the embodiments provided herein shall fall within the scope of the embodiments of the present application.

The present application is further described below with reference to specific examples.

Example 1: prescription information

The amounts of each formulation when the active ingredients are betamethasone and triamcinolone acetonide, respectively, are listed in example 1, with specific information as shown in table 1 below:

table 1 prescription information

Example 2: quality inspection

Example 2 samples of formulations 1 to 6 of example 1 were examined for encapsulation efficiency, in vitro release, cell activity, as shown in fig. 1 and table 2:

table 2 quality inspection of prescriptions

By examining the encapsulation efficiency, in vitro release, cell activity of the samples of formulas 1 to 6, it can be seen that:

the encapsulation rate of the samples of prescriptions 1 to 6 is not lower than 90%, which indicates that more active ingredients can be encapsulated in the carrier system of 6 prescription samples, and the loss of the active ingredients can be reduced.

In the in vitro release investigation of samples of prescriptions 1 to 6 for 72 hours, more than 90% of active ingredients can be released from 6 prescription samples, which indicates that the sample system is beneficial to improving the utilization rate of the active ingredients.

In the cell activity investigation of the samples of the prescriptions 1 to 6, the cell activity of the 6 prescriptions is lower than 80%, which indicates that the 6 prescriptions can effectively inhibit cell proliferation and reduce scar tissue generation.

Example 3: investigation of the amount and type of Phospholipids

The amount and type of phospholipids used in this test were examined using the sample of prescription 5 of example 1 as a control, and the specific contents are shown in fig. 2 and table 3:

TABLE 3 examination of the amounts and types of phospholipids

In example 3, the amount and type of the phospholipid were examined, and as shown in fig. 2, it can be seen from the test results that the type and amount of the phospholipid have an effect on the encapsulation efficiency of the sample, specifically, the following:

in formula 5-1, liposome was prepared using dioleoyl phosphatidylethanolamine and egg yolk lecithin, wherein the mass parts of dioleoyl phosphatidylethanolamine were the same as that of distearoyl phosphatidylethanolamine in formula 5, and the mass parts of soybean lecithin were the same as that of egg yolk lecithin in formula 5. As can be seen from the encapsulation efficiency, the liposome prepared from dioleoyl phosphatidylethanolamine and egg yolk lecithin had a poor encapsulation efficiency compared to formulation 5, and the formulation 5-1 sample did not encapsulate the active ingredient well.

Liposomes were prepared using only dioleoyl phosphatidylethanolamine in formulation 5-2, with samples having significantly lower encapsulation rates than 90%, indicating that the encapsulation of the active ingredient is not satisfactory using only dioleoyl phosphatidylethanolamine.

The distearoyl phosphatidyl ethanolamine and soybean lecithin of prescription 5-3 are used in small amounts, which is unfavorable for forming liposome and results in low encapsulation efficiency. The distearoyl phosphatidyl ethanolamine and soybean lecithin of prescription 5-4 are too high in dosage, and are also unfavorable for liposome, thereby affecting encapsulation.

When the prescription 5 sample is examined, the encapsulation rate can reach 90%, which shows that the prescription sample can well encapsulate the active ingredients and reduce the loss of the active ingredients.

Example 4: investigation of cholesterol usage

The test uses the sample of the prescription 5 of the example 1 as a control, and the cholesterol consumption is examined, and the specific contents are shown in fig. 3 and table 4:

TABLE 4 investigation of cholesterol usage

Example 4 the amount of cholesterol was examined and shown in figure 3.

No cholesterol was added to the formulations 5-5, and the sample showed poor encapsulation and severe loss of active ingredient. In the formulations 5-6, the encapsulation efficiency still does not reach 90% because the excessive amount of cholesterol affects the balance of the system.

Example 5: investigation of neutral fat type and amount

The test uses the prescription 5 sample of example 1 as a control to examine the type and amount of the neutral fat, and the specific contents are shown in fig. 4 and table 5:

table 5 screening and dose investigation of neutral fat

Example 5 the type and amount of neutral fat were examined, and as shown in fig. 4, it was found from the test results that the type and amount of neutral fat had a large influence on the degree of polymer dispersion of the sample.

In formulations 5-7, the same mass parts of palmitic acid triglyceride as the triolein in formulation 5 was used to prepare the samples, but the polymer dispersion index of the formulations 5-7 samples was as high as 0.3, indicating that the use of palmitic acid triglyceride was detrimental to system dispersion. The system dispersibility of the prescription 5 using triolein is close to 0.1, which shows that the system dispersibility is better, the agglomeration tendency is smaller, and the system uniformity is better, thereby being more beneficial to the release of the active ingredients.

The polymer dispersibility index of the formulations 5-8 is close to 3, which indicates that the too small dosage of triolein is unfavorable for system dispersion; the polymer dispersibility index of formulas 5-9 is similar to 3, but the large amount of triolein in formulas 5-9 indicates that excessive amount of triolein can cause system coagulation, resulting in poor system uniformity and thus being unfavorable for the release of active ingredients.

Example 6: investigation of the amount of specific targeting

The test uses the sample of the prescription 5 of the example 1 as a control to examine the amount of the hypertrophic scar fibroblast and keloid fibroblast, and the specific contents are shown in fig. 5 and table 6:

TABLE 6 investigation of specific targeting amounts

Example 6 is an examination of the amount of hypertrophic scar fibroblast and keloid fibroblast used. As shown in fig. 5.

The amounts of the hypertrophic scar fibroblast and keloid fibroblast in prescription 5-10, prescription 5 and prescription 5-11 are gradually increased. Experiments show that the scar detention rate of the prescription 5-10 is low, which indicates that the dosage of the hypertrophic scar fibroblast and the keloid fibroblast is low, and the detention of the active ingredients at the scar is not facilitated, so that the targeting and positioning of the affected part are not facilitated.

The scar retention rates of prescription 5 and prescription 5-11 are equal, not less than 70%, indicating that both prescription 5 and prescription 5-11 are beneficial for the active ingredient to remain in the scar. However, the amount of the hypertrophic scar fiber cell membrane and the keloid fiber cell membrane in the prescription 5-11 is close to 2 times of the amount of the hypertrophic scar fiber cell membrane and the keloid fiber cell membrane in the prescription 5, which easily causes relatively larger granularity of the system and is unfavorable for drug release.

Example 7: investigation of the amount of polyethylene glycol with double selenium bonds in the Phospholipids

The test uses the sample of the prescription 5 of the example 1 as a control, and examines the dosage of the phospholipid diselenide polyethylene glycol, and the specific content is shown in fig. 6 and table 7:

TABLE 7 investigation of the amount of polyethylene glycol used in phospholipid diselenide linkage

Example 7 is an examination of the amount of polyethylene glycol with a phospholipid diselenide bond, as shown in FIG. 6.

No phospholipid diselenide polyethylene glycol is added in the prescription 5-12, so that the prescription 5-12 sample has no burst release effect, so that the in-vitro release is low at 2 hours, and the inhibition of scar tissues is not facilitated. In the prescription 5-14, although the phospholipid diselenide polyethylene glycol is added, the dosage is small, the in vitro release is relatively low, the burst release effect of the active ingredient is not obvious, and the inhibition of scar tissues is also not facilitated.

In vitro release of prescription 5 and prescription 5-13 are basically consistent, but the dosage of the phospholipid diselenide polyethylene glycol in prescription 5-13 is higher, which is easy to cause poor uniformity of system particles, so that the dosage of the phospholipid diselenide polyethylene glycol in prescription 5 is relatively more reasonable.

Example 8: in vitro hemolysis test

Test sample: sample of recipe 5 in example 1.

Taking a blood sample of the rabbit ear vein of a healthy family, taking out fibrin by light stirring, adding a PBS solution, centrifuging, discarding the supernatant, and repeating the above operation for 4-5 times until the supernatant is basically free of obvious red. And diluting the obtained red blood cells with PBS solution to obtain a red blood cell suspension for later use.

Three equal portions of erythrocyte suspension were taken:

preparation of negative control group (PBS): adding a PBS solution to the first aliquot of red blood cell suspension;

preparation of positive control group (deionized water): adding deionized water to the second portion of the red blood cell suspension;

preparation of the sample set to be tested (prescription 5): adding the sample of prescription 5 to a third suspension of erythrocytes;

the negative control group, the positive control group and the sample group to be tested were incubated at 37℃for 4h and centrifuged. The supernatants of each group were individually taken in 96-well plates, absorbance was measured by an enzyme-labeled instrument (λ=570 nm) and the hemolysis rate was calculated.

As shown in fig. 7, the hemolysis rate of deionized water (positive control group) is close to 100%, the hemolysis rate of PBS solution (negative control group) is close to 0%, the hemolysis rate of the sample of prescription 5 is lower than <5%, which indicates that the sample of prescription 5 has almost no hemolysis on rabbit red blood cells, and the safety is good.

Example 9: in vitro Release test

Test sample: sample of recipe 5 in example 1.

Preparation of the sample set to be tested (prescription 5): the prescription 5 sample was placed in a dialysis bag. After the packaging, the mixture is placed into a centrifuge tube, and isotonic physiological saline is filled in the centrifuge tube.

Preparation of the original drug group: triamcinolone acetonide in an amount equivalent to the active ingredient of formula 5 of example 1 was placed in a dialysis bag. After the packaging, the mixture is placed into a centrifuge tube, and isotonic physiological saline is filled in the centrifuge tube.

The sample set and the drug substance set to be tested were oscillated at a constant speed (100 rpm) in a shaker at 37 ℃. The solution outside the dialysis bag was taken at the time points of 30min, 1h, 2h, 6h, 9h, 12h, 24h, 36h, 48h and 72h, respectively, and the equivalent amount of isotonic physiological saline was supplemented.

And measuring the concentration of the active ingredient dissolved at each time point of the sample group to be measured and the original medicine group, and calculating the in vitro release rate.

As shown in fig. 8, the outer layer of the sample group to be tested (prescription 5) is a cell membrane capable of sensing and responding to changes in the level of active oxygen (hypertrophic scar fibrous cell membrane and keloid fibrous cell membrane), and the inner layer is a liposome having a sustained release property. The hypertrophic scar fibroblast membrane and keloid fibroblast membrane carry active ingredients, and after needleless injection into the scar, corresponding cells can be targeted in a short time, the carried active ingredients can be quickly released in response to the microenvironment of higher active oxygen in the scar, and then the liposome inside is released to stabilize and slowly release the active ingredients. The distearoyl phosphatidylethanolamine is matched with the liposome, so that the solubility of the active ingredient can be improved, and the in-vitro release is relatively high.

However, triamcinolone acetonide in the drug substance group has low in vitro release due to its lack of cell membranes capable of sensing and responding to changes in active oxygen levels and its non-liposomal form, which is poor in solubility.

Example 10: anti-rabbit ear scar test

New Zealand rabbits were randomly equally divided into normal skin, no treatment, needle injection, needle-free injection and commercial groups.

The rabbit ear ventral scar model was established for New Zealand rabbits in the no-treatment, needle-injected, needleless, and commercially available groups.

The sample of prescription 5 in example 1, 20mg/ml, was injected into the needle injection group by means of a needle syringe (disposable syringe with needle).

The sample of prescription 5 in example 1 was injected into the needleless injection group by a needleless injector at 20 mg/ml.

The commercial group was injected with a commercial triamcinolone acetonide injection via a needle syringe.

Wherein the administration amounts and the administration concentrations of the needle-containing injection group, the needleless injection group and the commercial group are consistent.

Injections were continued 2 times at 1 week intervals. The scar efficacy was evaluated after one week post injection 2. The thickness of the blood stasis tissue and normal skin dermis in hematoxylin-eosin tissue sections was measured and the epilepsy index was calculated.

As shown in fig. 9, the scar index was significantly increased in the untreated group without any treatment after modeling compared to the normal skin group. The scar index was relatively higher in the needle-injected, needleless and commercially available groups compared to the normal skin group after treatment, but significantly lower in the non-treated group.

Since the needle-injected group and the commercial group were administered using a syringe with an injection needle, the scar index was still high in both groups compared to the needleless injection group. Thus, needle injections can be seen to cause some damage to tissue.

As can be seen from fig. 9, the needle-injected group and the needleless injected group have a better scar-inhibiting effect, but the scar-inhibiting effect is more remarkable by the administration of needleless injection.

It should also be noted that the term "comprises," "comprising," or any other variation thereof is intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising at least one of the elements" does not exclude the presence of additional identical elements in a process, method, article or apparatus that comprises the element.

In this specification, each embodiment is described in a progressive manner, and identical and similar parts of each embodiment are all referred to each other, and each embodiment mainly describes differences from other embodiments.

Finally, it should be noted that the foregoing description is only an example of the present application, and is merely for illustrating the technical solution of the present invention, not for limiting the present application. Various modifications and changes may be made to the present application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc. which are within the spirit and principles of the present application are intended to be included within the scope of the claims of the present application.

Claims

1. A composition for needle-free transdermal injection comprising:

the ratio of the mass of the scar inhibitor to the total mass of the specific targeting agent, the phospholipid, the cholesterol and the neutral fat is 1:15-24;

the mass ratio of the phospholipid to the neutral fat is 1:2.5-7.5;

the mass ratio of the phospholipid to the cholesterol is 1:1.25-3;

the concentration of the scar inhibitor in the composition for needleless percutaneous injection is 0.25-1mg/ml;

the specific target is selected from the group consisting of: a proliferative scar fibroblast membrane and/or a keloid fibroblast membrane;

the scar inhibitor is selected from the group consisting of: triamcinolone acetonide or betamethasone.

2. The composition for needle-free transdermal injection according to claim 1, wherein,

when the specific target comprises the hypertrophic scar fibroblast membrane and the keloid fibroblast membrane, the mass ratio of the hypertrophic scar fibroblast membrane to the keloid fibroblast membrane is 1:1.

3. The composition for needle-free transdermal injection according to claim 1, wherein,

the phospholipid comprises: electronegative phospholipids and ampholytic phospholipids;

the mass ratio of the electronegative phospholipid to the ampholytic phospholipid is 1:0.25-0.5.

4. A composition for needleless percutaneous injection according to claim 3, wherein,

when the electronegative phospholipid is distearoyl phosphatidylethanolamine and the ampholytic phospholipid is soybean lecithin, the neutral fat comprises glycerol trioleate.

5. The composition for needle-free transdermal injection according to any one of claim 1 to 4,

the mass ratio of the phospholipid diselenide polyethylene glycol to the specific targeting agent is 1:10.