Isotretinoin oil, preparation method and application thereof

Abstract

The present invention relates to the technical field of new dosage forms of drugs, and in particular to an isotretinoin oil, a preparation method thereof and an application thereof. The isotretinoin oil is composed of the following components by mass: 97.5-99.9 parts of peroxidized triglycerides, 0.01-0.25 parts of isotretinoin; the peroxidized triglycerides are prepared by oxidation of triglycerides; the triglycerides mainly include oleic triglycerides, dioleic acid-palmitic acid triglycerides, dioleic acid-stearic acid triglycerides, dioleic acid-linoleic acid triglycerides, and linoleic acid triglycerides. The peroxide value of the peroxidized triglycerides is 160-240 meq / kg; the acid value is 5-10 mg / g. The isotretinoin oil of the present invention can treat mild and moderate acne, seborrheic dermatitis, trichoderma dermatitis, keratosis pilaris, and other skin diseases caused by excessive keratinization under natural light conditions; it is safe and effective for external use. It can also be used to control microacne and prevent the occurrence of acne.

Description

Technical Field

[0001] The present invention relates to the technical field of new drug dosage forms, and in particular to an isotretinoin oil preparation and a preparation method and application thereof. Background Art

[0002] Acne is a chronic, immune-mediated inflammatory disease that affects the pilosebaceous glands. In the early stages, acne is manifested by comedones and papules. In the middle stages, pustules and nodules gradually form. In the late stages, the skin is severely damaged, with persistent pigmentation, scars and other irreversible skin damage. The clinical prevalence is high, and safe and effective topical medications are urgently needed.

[0003] Isotretinoin is a type of vitamin A and an isomer of all-trans retinoic acid. Isotretinoin can shrink sebaceous gland tissue, inhibit sebaceous gland activity, and reduce sebaceous gland secretion, and can be used to treat acne. Oral administration of isotretinoin can cause dryness and desquamation of the skin and mucous membranes, and may cause musculoskeletal pain, elevated blood lipids, and abnormal liver function. Currently, the marketed topical isotretinoin preparations include gels, ointment preparations, etc., but no oil preparations. Isotretinoin can improve the keratinization of the hair follicle duct and dissolve acne.

[0004] For mild acne, oral isotretinoin is generally not used for treatment. The main treatment is external preparations. However, adverse reactions such as erythema, itching, burning, dryness, and desquamation are prone to occur in clinical treatment of mild to moderate acne. Isotretinoin has photosensitivity reactions. External isotretinoin preparations must be used at night. Isotretinoin may cause allergic reactions in the human body under light stimulation, such as skin itching, erythema, and edema. Because of the irritation, it can only be applied locally.

[0005] There are some ozone oil products in the prior art, but none of them are isotretinoin oil products. For example, CN202010416020.2 provides a compound ozone oil and its preparation method and application. The compound ozone oil includes 60 to 90 parts by weight of ozonated camellia oil, 1 to 40 parts by weight of breviscapus oil, and 1 to 40 parts by weight of honeysuckle oil, wherein the ozonated camellia oil is obtained by ozone curing reaction of camellia oil and ozone. N201810303785.8 provides compound ozone oil, compound ozone oil products and applications. The compound ozone oil contains 0.5-5 parts by weight of ozonated camellia oil, 0.2-4 parts by weight of ozonated lithospermum oil, 0.6-1 parts by weight of Sophora flavescens and 0.6-1 parts by weight of Bletilla striata, wherein the ozonated camellia oil and the ozonated lithospermum oil are obtained by ozone curing reaction of camellia oil and lithospermum oil with ozone, respectively. The above invention does not involve the application of acne and is prone to side effects such as irritation, redness and swelling.

[0006] There is no suitable isotretinoin oil product in the prior art, and it is of great significance to develop an isotretinoin oil product. Summary of the invention

[0007] The present invention aims to provide an isotretinoin oil preparation with good therapeutic effect and small side effects, and a preparation method and application thereof.

[0008] In order to achieve the above object, the technical solution of the present invention is as follows:

[0009] An isotretinoin oil preparation is composed of the following components in parts by mass: 99.75-99.99 parts of peroxidized triglyceride and 0.01-0.25 parts of isotretinoin; the peroxidized triglyceride is prepared by oxidation reaction of triglyceride; the triglyceride includes one or more of oleic triglyceride, dioleic acid-palmitic acid triglyceride, dioleic acid-stearic acid triglyceride, dioleic acid-linoleic acid triglyceride and linoleic acid triglyceride; the peroxide value of the peroxidized triglyceride should be 160-240 meq / kg; and the acid value of the peroxidized triglyceride is 5-10 mg / g.

[0010] If the peroxide value of the peroxidized triglyceride is too high, it will be more likely to cause irritation, while if it is too low, the anti-inflammatory and bactericidal effects will be insufficient.

[0011] If the acid value of the peroxidized triglyceride is too high, it will cause irritation, and if it is too low, it will have no anti-inflammatory and bactericidal effect.

[0012] In a preferred embodiment, the amount of isotretinoin is 0.05 parts.

[0013] In a preferred embodiment, the ozone absorption of the peroxidized triglyceride is 40-80 mg / g.

[0014] Based on the same invention, the present invention also claims a method for preparing the isotretinoin oil, comprising the following steps:

[0015] Step 1: passing a mixed gas into oleic acid triglyceride to carry out an oxidation reaction to obtain peroxidized triglyceride; the mixed gas is a mixed gas of ozone and oxygen;

[0016] Step 2: Mix isotretinoin and peroxidized triglyceride to obtain isotretinoin oil.

[0017] In a preferred embodiment, the mixed gas involved in the oxidation reaction does not contain nitrogen oxides. In a preferred embodiment, the mixed gas is introduced into the oleic acid triglyceride at a flow rate of 0.5-1.5 L / min.

[0018] The mixed gas is introduced into the bottom of the oleic triglyceride to fully contact the oleic triglyceride; if the speed is too fast, the reaction is incomplete, and if the speed is too slow, the amount of the mixed gas is insufficient.

[0019] In a preferred embodiment, in the mixed gas of step 1, the volume concentration of ozone is 1.4%-4.7% (v / v), and the volume concentration of oxygen is 95.3%-98.6% (v / v).

[0020] In a preferred embodiment, the reaction time of step 1 is 5-12 hours.

[0021] In a preferred embodiment, if the peroxide value, acid value and absorption of the peroxidized triglyceride are within the qualified range, the peroxidized triglyceride is qualified.

[0022] In a preferred embodiment, the reaction temperature of step 1 is 15°C-25°C, and the rotation speed is greater than 300 rpm.

[0023] If the reaction temperature of step 1 is too high, by-products will be formed, resulting in lower product purity, while if the temperature is too low, the reaction efficiency will be affected.

[0024] The length of the reaction time in step one is evaluated based on the ozone absorption and the peroxide value, and the reaction needs to meet the peroxide value requirement.

[0025] In a preferred embodiment, in step 2, isotretinoin is mixed with peroxidized triglyceride to obtain a uniform and stable isotretinoin oil.

[0026] In a preferred embodiment, the rotation speed of step 2 should be greater than 400 rpm.

[0027] The rotation speed in step 2 is too low, which affects the ozone absorption efficiency.

[0028] Based on the same invention, the present invention also claims to protect the use of the isotretinoin oil in the preparation of drugs for treating skin diseases.

[0029] In a preferred embodiment, the skin diseases include mild mild, moderate acne, seborrheic dermatitis, trichophyton dermatitis, keratosis pilaris, and other skin diseases caused by excessive keratinization; the topical application is safe and effective. It can also be used to control microacne and prevent the occurrence of acne.

[0030] Compared with the prior art, the advantages of the present invention are:

[0031] 1. The present invention provides an isotretinoin oil, which can treat skin diseases and is safe and effective for external use.

[0032] 2. This study shows that the treatment results of isotretinoin oil for skin diseases show that the total effective rate of 29 patients with skin diseases after one month of treatment is 89.65%. Isotretinoin oil is safe and effective for external use in the treatment of skin diseases, and has fewer side effects than other isotretinoin gel preparations.

[0033] 3. The isotretinoin oil of the present invention has low irritation and adverse reactions, and can reduce or avoid photosensitivity reactions such as erythema and itching caused by isotretinoin. The limitations of the use time and use environment of isotretinoin in the process of external application are solved. The isotretinoin oil contains peroxidized triglyceride, which enhances the antibacterial effect of the oil on other pathogenic bacteria such as Propionibacterium acnes, and can enhance the therapeutic effect of the isotretinoin oil. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 The following are the clinical application results of the isotretinoin oil of Example 1 in the treatment of acne. DETAILED DESCRIPTION

[0035] The following will be combined with the attached table in the embodiment of the present invention to clearly and completely describe the technical solutions in the embodiment of the present invention. Obviously, the described embodiment is only a part of the embodiment of the present invention, not all of the embodiments. Based on the embodiment of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0036] Example 1

[0037] An isotretinoin oil comprises the following components in parts by weight: 99.95 parts of peroxidized triglyceride and 0.05 parts of isotretinoin; the peroxidized triglyceride is prepared from triglyceride through an oxidation process; and the mixed gas involved in the oxidation process does not contain nitrogen oxides.

[0038] The preparation method of the isotretinoin oil comprises the following steps:

[0039] Step 1: ozone / oxygen mixed gas is passed into 350g oleic acid triglyceride at a flow rate of 1L / min, the ozone gas concentration is 2.8% (v / v), stirred at 400rpm, reacted at 20°C for 7h, and peroxidized triglyceride is obtained; at the end of the reaction, the peroxide value of peroxidized triglyceride should be 200meq / kg. The acid value of peroxidized triglyceride is 5mg / g. The absorption of ozone in peroxidized triglyceride is 60mg / g. In the mixed gas, the volume concentration of ozone is 2.3% (v / v), and the volume concentration of oxygen is 97.7% (v / v). Step 2: Mix isotretinoin and peroxidized triglyceride, stir at 450rpm, and react for 7h to obtain isotretinoin oil with uniform and stable properties.

[0040] Comparative Example 1

[0041] On the basis of Example 1, the reaction time of step 1 was adjusted to adjust the peroxide value of peroxidized triglyceride to 140 meq / kg, thereby obtaining isotretinoin oil 2.

[0042] Comparative Example 2

[0043] On the basis of Example 1, the reaction time of step 1 was adjusted to adjust the peroxide value of peroxidized triglyceride to 260 meq / kg, thereby obtaining isotretinoin oil 3.

[0044] Comparative Example 3

[0045] On the basis of Example 1, the stirring speed in step 1 was adjusted to 500 rpm, and the acid value of peroxidized triglyceride was adjusted to 12 mg / g, thereby obtaining isotretinoin oil 4.

[0046] Comparative Example 4

[0047] On the basis of Example 1, the stirring speed in step 1 was adjusted to 200 rpm, and the acid value of peroxidized triglyceride was adjusted to 3 mg / g, thereby obtaining isotretinoin oil 5.

[0048] Comparative Example 5

[0049] On the basis of Example 1, the ozone concentration was adjusted to 1.0% (v / v) and the ozone absorption of peroxidized triglyceride was adjusted to 30 mg / g, thereby obtaining isotretinoin oil preparation 6.

[0050] Comparative Example 6

[0051] On the basis of Example 1, the ozone concentration was adjusted to 5.0% (v / v) and the ozone absorption of peroxidized triglyceride was adjusted to 90 mg / g, thereby obtaining isotretinoin oil preparation 7.

[0052] Comparative Example 7

[0053] Based on Example 1, the reaction temperature of step 1 was adjusted from 20°C to 40°C.

[0054] Comparative Example 8

[0055] Based on Example 1, the reaction temperature of step 1 was adjusted from 20°C to 5°C.

[0056] Comparative Example 9

[0057] 99.95 parts of oleic triglyceride and 0.05 parts of isotretinoin are mixed, and the isotretinoin is stirred at 450 rpm for 7 hours to obtain a uniform and stable isotretinoin oil.

[0058] Example 2

[0059] An isotretinoin oil comprises the following components by mass: 99.90 parts of peroxidized triglyceride and 0.10 parts of isotretinoin; the peroxidized triglyceride is prepared by an oxidation process of triglyceride; the mixed gas involved in the oxidation process does not contain nitrogen oxides. The peroxide value of the peroxidized triglyceride is 160 meq / kg. The acid value of the peroxidized triglyceride is 8 mg / g. The ozone absorption amount of the peroxidized triglyceride is 40 mg / g.

[0060] The preparation method of the isotretinoin oil comprises the following steps:

[0061] Step 1: ozone / oxygen mixed gas is passed into 350 g of oleic acid triglyceride at a flow rate of 1 L / min, stirred at 400 rpm, and reacted at 20° C. for 7 h to obtain peroxidized triglyceride; in the mixed gas, the volume concentration of ozone is 1.4% (v / v), and the volume concentration of oxygen is 98.6% (v / v).

[0062] Step 2: Under stirring, add isotretinoin to peroxidized triglyceride, stir at 450 rpm, and react for 7 hours to obtain isotretinoin oil.

[0063] Example 3

[0064] An isotretinoin oil comprises the following components by mass: 99.98 parts of peroxidized triglyceride and 0.02 parts of isotretinoin; the peroxidized triglyceride is obtained by ozone curing reaction of oleic triglyceride and ozone. The mixed gas involved in the oxidation process does not contain nitrogen oxides. The peroxide value of the peroxidized triglyceride should be 240 meq / kg. The acid value of the peroxidized triglyceride is 10 mg / g. The absorption of ozone in the peroxidized triglyceride is 80 mg / g.

[0065] The preparation method of the isotretinoin oil comprises the following steps:

[0066] Step 1: ozone / oxygen mixed gas is passed into 350 g of oleic acid triglyceride at a flow rate of 1 L / min, stirred at 400 rpm, and reacted at 20° C. for 7 h to obtain peroxidized triglyceride; in the mixed gas, the volume concentration of ozone is 2.8% (v / v), and the volume concentration of oxygen is 97.2% (v / v).

[0067] Step 2: Under stirring, add isotretinoin to peroxidized triglyceride, stir at 450 rpm, and react for 7 hours to obtain isotretinoin oil.

[0068] Performance Testing

[0069] 1. Antibacterial effect of isotretinoin oil on Propionibacterium acnes

[0070] The antibacterial effect of isotretinoin oil was studied using Propionibacterium acnes as the test bacteria.

[0071] Take a 72-hour fresh slant culture of the test bacteria, wash it with sterile saline, and dilute it with sterile saline to about 5.0×10 5 CFU / mL~5.0×10 6 CFU / mL was used to prepare bacterial suspension for later use.

[0072] Take a sterile centrifuge tube, add 5.0mL of isotretinoin oil first, place it in a 20℃±1℃ water bath for 5 minutes, then add 0.1mL of the test bacterial suspension, mix quickly and start the time immediately.

[0073] When the test bacteria and the sample interact, take 1.0 mL of the test bacteria and sample mixture and inoculate two plates respectively, pour the culture medium, and count the viable bacteria. At the same time, replace the sample with sterile saline and perform a parallel test as a positive control. The number of colonies recovered in the positive control is 1.0×10 4 CFU / mL~9.0×10 4 CFU / mL. Sterile saline and culture medium were used as negative controls. All test groups and positive control groups were cultured at 36℃±1℃ for 72h to observe the results; the test was repeated 3 times and the inhibition rate was calculated.

[0074] Calculation method of antibacterial rate: X = (N C -N S ) / N C *100%

[0075] Where X is the antibacterial rate %; N C is the average colony count of the positive control group, cfu / mL; N S is the average colony count of the test group, cfu / mL.

[0076] Table 1 Antibacterial results of isotretinoin oil on Propionibacterium acnes

[0077]

[0078]

[0079] Note: The number of bacteria in the positive control group was 4.37×10 4 CFU / ml, no colony growth in negative control

[0080] From the above antibacterial test results, it can be seen that the antibacterial rate of Example 1, Example 2, and Example 3 can reach more than 95% after acting on Propionibacterium acnes for 10 minutes. However, the antibacterial effect of Comparative Examples 1, 4, 5, 8, and 9 is not good, and the antibacterial effect cannot reach 100% after acting on Propionibacterium acnes for 30 minutes. Comparative Examples 2, 3, and 6 can reach 100% after acting on Propionibacterium acnes for 30 minutes.

[0081] Considering that the stronger the antibacterial effect of isotretinoin oil on Propionibacterium acnes, the better the effect of treating acne, Example 1 and Comparative Examples 2, 3, and 6 were selected for safety tests to screen oils with better safety for clinical observation.

[0082] 2 Animal irritation experiment of isotretinoin oil

[0083] 2.1 Experimental Animal Preparation

[0084] Albino guinea pigs (350g-450g), 25, half male and half female. Before the test, the animals were cultured in the experimental animal room for 3 days, and the hair on the dorsal area was removed for 24 hours, with the hair removal area of ​​4cm×4cm. Before the drug administration, check whether the hair removal skin is damaged, and remove the experimental animals with damaged skin. Use a puncture needle to make a "well" shape (sandpaper grinding) on ​​the drug administration site, and the bleeding is the limit.

[0085] 2.2 Experimental Animal Grouping and Dosing

[0086] The experimental animals were divided into 5 groups. Each group had 5 animals. Four experimental groups were set up, and the experimental groups were smeared with the isotretinoin oil prepared in Example 1, Comparative Examples 2, 3, and 6, respectively. A blank control group was also set up, and the administration site was covered with two layers of gauze and one layer of cellophane, and then fixed with non-irritating adhesive tape and bandage, and applied for 4 hours.

[0087] 2.3 Experimental observation, scoring and evaluation

[0088] Acute skin irritation test: Administer the drug once. After application, remove the test substance and clean the application site with warm water. Observe the application site with naked eyes and record the presence of erythema and edema at 1, 24, 48 and 72 hours after removal of the test substance. According to the scoring standard table 2 and the evaluation standard table 3, make a comprehensive evaluation of the average score of the test animals and record the weight change of the test animals.

[0089] Multiple skin irritation test: Continuously administer the drug to the same site, once a day and apply for 4 hours, for 14 consecutive days. Starting from the second day, the hair should be trimmed before each application, and the residual drug should be removed with clean water. After each application, remove the test substance and clean the administration site with warm water. 1, 24, 48, 72, 96, 120, 144, 168 hours after the last application and removal of the test substance, observe and record the presence of erythema and edema at the application site with the naked eye, and record the weight changes of the test animals. According to the scoring standard table 2 and the evaluation standard table 3, the average value of the test animal scores is comprehensively evaluated.

[0090] Table 2 Skin irritation response scoring criteria

[0091]

[0092] Table 3 Evaluation criteria for skin irritation intensity

[0093] Integral mean evaluate 0-0.49 Non-irritating 0.5-2.99 Mild irritant 3.0-5.99 Moderate irritation 6.0-8.00 Strong irritation

[0094] 2.4 Test results

[0095] Each group was tested and the scoring results were recorded as shown in Table 4, Table 5, and Table 6. The scoring results of the acute skin irritation experiment showed that the isotretinoin oil prepared in Example 1 was non-irritating, the isotretinoin oils of Comparative Examples 2, 3, and 6 were mildly irritating after 1 hour, Comparative Examples 2 and 3 recovered to non-irritating after 24 hours, and Comparative Example 6 recovered to non-irritating after 48 hours.

[0096] In multiple skin irritation experiments, the isotretinoin oil prepared in Example 1 showed mild irritation after 1 hour and recovered to no irritation after 72 hours. However, the comparative examples 2, 3, and 6 showed moderate irritation after 1 hour and still had irritation after 72 hours.

[0097] Table 4 Skin irritation reaction scoring results (acute skin irritation test) n = 5

[0098]

[0099] Table 5 Skin irritation reaction scoring results (multiple skin irritation tests) n = 5

[0100]

[0101] Table 6 Skin irritation reaction scoring results (multiple skin irritation tests) n = 5

[0102]

[0103] 2.5 Experimental conclusion

[0104] The experimental results show that Example 1 has better safety than Comparative Examples 2, 3, and 6 in the irritation experiment. The acute irritation experiment showed no irritation, and the multiple irritation experiment showed mild irritation in 1 hour, but the irritation can be recovered. Comparative Examples 2, 3, and 6 showed mild irritation in the single irritation experiment, and moderate irritation in multiple irritations, and the irritation was difficult to recover. It can be seen that Example 1 has better safety than the comparative examples.

[0105] 3. Human skin irritation test of isotretinoin oil

[0106] 3.1 Experimental plan

[0107] Thirty volunteers aged 18-60 who met the test requirements were selected as subjects. The following subjects were excluded: those who used antihistamines in the past week or immunosuppressants in the past month, those who used any anti-inflammatory drugs on the test site in the past two months, those who had inflammatory skin diseases that were not clinically cured, insulin-dependent diabetes patients, asthma or other chronic respiratory diseases being treated, those who received anti-cancer chemotherapy in the past 6 months, immunodeficiency or autoimmune disease patients, breastfeeding or pregnant women, those whose skin test sites had scars, pigments, atrophy, port wine stains or other blemishes that affected the determination of the test results, those who participated in other clinical trial researchers, those with highly sensitive constitutions, non-voluntary participants or those who could not complete the specified content according to the test requirements.

[0108] The flexed side of the forearm was used as the test site, with an area of ​​3×3cm 2 , the test site should be kept dry and avoid contact with other topical preparations. 0.05g of the test substance was evenly applied to the test site twice a day (once in the morning and once in the afternoon under natural light) for 7 consecutive days, and the skin reaction was observed at the same time. If a skin reaction of 3 points or more appeared during this process, the experiment was stopped. The subject's left arm was smeared with the isotretinoin oil prepared in Example 1, and the right arm was smeared with the isotretinoin oil prepared in Example 2. The skin reaction was observed according to Table 7, and the results were recorded.

[0109] If there are 5 or more cases of Grade 1 adverse skin reactions (including 5 cases), 2 cases of Grade 2 adverse skin reactions (including 2 cases) among 30 subjects, or 1 or more cases of any Grade 3 or above adverse skin reactions (including 1 case) occur, the test substance is judged to have obvious adverse reactions to humans.

[0110] Table 7 Evaluation criteria for skin reactions to repeated open smear test (clinical manifestations)

[0111]

[0112] 3.2 Experimental Results

[0113] 30 subjects applied it continuously for 7 days, and observed the skin reactions of the left and right arms as recorded in Table 8. The summary statistics according to the scoring levels in Table 8 are shown in Table 9. There were 2 cases of grade 1 adverse reactions to the isotretinoin oil prepared in Example 1, and 4 cases of grade 1 adverse reactions to the isotretinoin oil prepared in Example 2. No subject had grade 2 or higher adverse reactions in either sample. There were 28 cases of negative reactions to Example 1, and 26 cases of negative reactions to Example 2.

[0114] Table 8 Test score results for each subject

[0115]

[0116]

[0117] Table 9 Summary of human safety test results

[0118]

[0119] 3.3 Experimental Conclusion

[0120] According to the human safety test results, no obvious adverse reactions occurred in Examples 1 and 2. No test subjects developed erythema after using the isotretinoin oil under normal light conditions during the day, indicating that the isotretinoin oil can alleviate irritation reactions such as erythema caused by the photosensitivity reaction of isotretinoin. Example 3 also had no adverse reactions.

[0121] 4 Clinical application effect study of isotretinoin oil in the treatment of acne vulgaris

[0122] 4.1 Research Methods

[0123] The subjects were confirmed acne patients aged between 16 and 45 years old. The patients were divided into an observation group and a control group, with 30 cases in each group. There was no significant difference in the basic data of the two groups of patients, and they were comparable.

[0124] Inclusion criteria for patients with acne vulgaris: patients diagnosed with acne vulgaris in accordance with the relevant diagnostic criteria for acne vulgaris in the Chinese Journal of Clinical Dermatology; patients with mild to moderate acne of grade I to III according to the Pillsbuny grading standard. Patients with facial acne, no cognitive impairment, good communication skills, high treatment compliance, and informed consent for treatment.

[0125] Exclusion criteria: patients who have recently received relevant treatment or used isotretinoin or antibiotics; patients with severe liver and kidney dysfunction, and patients with mental illness.

[0126] Treatment method: The observation group patients applied the isotretinoin oil prepared by the method of Example 1, once a day, under normal light conditions; the control group 1 patients applied isotretinoin erythromycin gel (Sinopharm Group Zhonglian Pharmaceutical Co., Ltd., National Medicine Standard H20080404, 10g / tube), once a day, applied an appropriate amount on the rash before going to bed, and avoided or minimized exposure to sunlight or light tubes after medication. After 4 weeks of treatment, the rash subsided in the two groups of patients to evaluate the clinical efficacy.

[0127] Clinical efficacy index: Count the number of skin lesions such as acne and papules before and after treatment. Efficacy index = (number of skin lesions before treatment - number of skin lesions after treatment) / number of skin lesions before treatment × 100%. Basically cured: efficacy index ≥ 90%, markedly effective: 60% ≤ efficacy index < 90%; effective: 20% ≤ efficacy index < 60%. Effective rate = (number of cured cases + number of markedly effective cases + number of effective cases) / total number of cases × 100%.

[0128] 4.2 Research Results

[0129] Of the 60 patients, 57 completed the 4-week treatment, 2 patients dropped out of the control group, and 1 patient dropped out of the observation group. The total effective rates of the observation group and the control group were 89.65% and 85.71%, respectively. In the observation group, 9 patients were cured, 8 patients were markedly effective, and 9 patients were effective. In the control group, 8 patients were cured, 9 patients were markedly effective, and 8 patients were effective. The number of cured cases in the observation group was higher than that in the control group. The results are shown in Tables 10 and Figure 1 The incidence of adverse reactions in the observation group and the control group was 6.89% and 14.28%, respectively. The number of patients with adverse reactions such as itching and tingling in the observation group was less than that in the control group, as shown in Table 11.

[0130] Table 10 Comparison of clinical efficacy between the two groups of patients

[0131]

[0132]

[0133] Table 11 Adverse reactions in the two groups of patients

[0134] Group Desquamation erythema Itching tingling Adverse reaction rate (%) Observation group (n=29) 0 1 1 0 6.89 Control group (n=28) 0 1 2 1 14.28

[0135] 4.3 Research Conclusions

[0136] The results show that the topical isotretinoin oil prepared in Example 1 is effective in treating mild to moderate acne, with an effective rate of up to 89.65%. The incidence of side effects is lower than that of the existing isotretinoin erythromycin gel. Peroxidized triglyceride can effectively kill the pathogenic bacteria Propionibacterium acnes. It can replace the antibacterial effect of erythromycin in isotretinoin erythromycin gel. Isotretinoin oil can repair the skin barrier and avoid problems such as erythema and itching caused by the photosensitivity reaction of isotretinoin. The problem of being restricted to use only at night due to photosensitivity reaction is solved. At the same time, isotretinoin oil has few adverse reactions and can be used on a large area, solving the problem that isotretinoin can only be applied on a small scale in the past.

[0137] The above description is only an implementation mode of the present invention. It should be pointed out that, for ordinary technicians in this field, improvements can be made without departing from the creative concept of the present invention, but these all belong to the protection scope of the present invention.

Claims

1. An isotretinoin oil, characterized in that: The invention is composed of the following components by mass: 97.5-99.9 parts of peroxidized triglyceride and 0.01-0.25 parts of isotretinoin; the peroxidized triglyceride is prepared by an oxidation process of triglyceride; the steps are: passing a mixed gas into oleic triglyceride for oxidation reaction to obtain peroxidized triglyceride; the mixed gas is a mixed gas of ozone and oxygen; the reaction temperature is 15°C-25°C; The triglyceride comprises one or more of oleic triglyceride, dioleic acid palmitic acid triglyceride, dioleic acid stearic acid triglyceride, dioleic acid linoleic acid triglyceride, and linoleic acid triglyceride; the peroxide value of the peroxidized triglyceride is 160-240 meq / kg; the acid value is 5-10 mg / g; and the ozone absorption capacity of the peroxidized triglyceride is 40-80 mg / g.

2. The isotretinoin oil according to claim 1, characterized in that Isotretinoin is 0.05 parts.

3. The method for preparing the isotretinoin oil according to claim 1 or 2, characterized in that: The following steps are involved: Step 1: introducing a mixed gas into oleic acid triglyceride to carry out an oxidation reaction to obtain peroxidized triglyceride; the mixed gas is a mixed gas of ozone and oxygen; Step 2: Mix isotretinoin and peroxidized triglyceride to obtain isotretinoin oil.

4. The preparation method according to claim 3, characterized in that: The reaction temperature of step 1 is 15°C-25°C, the rotation speed is greater than 300rpm; and the reaction time is 5-12h.

5. The preparation method according to claim 3, characterized in that: The mixed gas does not contain nitrogen oxides.

6. The preparation method according to claim 3, characterized in that: The mixed gas is introduced into oleic acid triglyceride at a flow rate of 0.5-1.5 L / min.

7. The preparation method according to claim 3, characterized in that: In the mixed gas, the volume concentration of ozone is 1.4%-4.7%, and the volume concentration of oxygen is 95.3%-98.6%.

8. The preparation method according to claim 3, characterized in that: The rotation speed of step 2 should be greater than 400 rpm.

9. Use of the isotretinoin oil according to claim 1 or 2 or the isotretinoin oil prepared by the preparation method according to any one of claims 3 to 8 in preparing a medicament for treating skin diseases, wherein the skin diseases are mild or moderate acne, seborrheic dermatitis, folliculitis dermatitis, and keratosis pilaris.

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