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CN-122005438-A - Tanshinone I intrauterine sustained-release medicament for treating gynecological tumors and application thereof

CN122005438ACN 122005438 ACN122005438 ACN 122005438ACN-122005438-A

Abstract

The invention discloses a tanshinone I intrauterine sustained-release medicament for treating gynecological tumors and application thereof, wherein the tanshinone I is prepared into a nano-structure lipid carrier with the average particle size of 100-200 nm, so that the water solubility and the biomembrane permeability of the carrier are obviously improved, and the carrier is further loaded in a biodegradable polymer sustained-release rod capable of being placed in a uterine cavity. The slow release rod can degrade and release medicines in the intrauterine environment, and realizes local, long-acting and targeted administration to focus positions. In vitro cell experiments prove that the preparation has obviously stronger inhibition effect on hysteromyoma cells than toxicity on normal myometrium cells, and has a selectivity index of more than 2, thereby solving the problems of poor solubility of tanshinone I and weak targeting of systemic administration, and having the outstanding advantages of high efficiency, low toxicity and good patient compliance.

Inventors

  • YANG JINGQI

Assignees

  • 杨景淇

Dates

Publication Date
20260512
Application Date
20260212

Claims (9)

  1. 1. The tanshinone I intrauterine sustained release medicament for treating gynecological tumors is characterized by comprising a tanshinone I nanostructure lipid carrier and a biodegradable polymer sustained release rod loaded with the tanshinone I nanostructure lipid carrier; wherein the tanshinone I nanostructured lipid carrier comprises tanshinone I with the average particle diameter of 100-200 nm, solid lipid and an emulsifier, and the encapsulation rate is not lower than 70%; The biodegradable polymer slow release rod is of a rod-shaped structure suitable for being placed in a uterine cavity, and can degrade and release the tanshinone I nanostructure lipid carrier under the environment of the uterine cavity, so that the local slow release of the medicine is realized.
  2. 2. The tanshinone I intrauterine sustained release preparation for treating gynecological tumors according to claim 1 wherein the solid lipid is selected from one or more of glyceryl monostearate, glyceryl behenate and glyceryl stearate, and the emulsifying agent is selected from one or more of soybean phospholipid, lecithin and poloxamer 188.
  3. 3. The tanshinone I intrauterine sustained release preparation for treating gynecological tumors according to claim 1 wherein the tanshinone I nanostructured lipid carrier is prepared by high-pressure homogenization or microemulsion, and Zeta potential is-30 mV to-5 mV during the preparation.
  4. 4. The tanshinone I intrauterine sustained release preparation for treating gynecological tumors of claim 1 wherein the biodegradable polymer sustained release rod has a uterine-like shape with a length of 30mm to 70mm, a width of 30mm to 65mm and a thickness of 0.1mm to 2 mm.
  5. 5. The tanshinone I intrauterine sustained release preparation for treating gynecological tumors according to claim 1 wherein the biodegradable polymer sustained release stick comprises an outer coating composed of a drug-loaded degradable micro-nanofiber membrane and an inner core membrane prepared from a water-swellable biodegradable polymer material encapsulated in the outer coating.
  6. 6. The tanshinone I intrauterine sustained release preparation for treating gynecological tumors according to claim 5 wherein the degradable micro-nano fibrous membrane is prepared by adopting an electrostatic spinning technology, the material is selected from one or more of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone and degradable polyurethane, and the material of the inner core membrane is selected from one or more of alginate, hyaluronic acid, chitosan and carboxymethyl chitosan.
  7. 7. The tanshinone I intrauterine sustained release preparation for treating gynecological tumors according to claim 1 wherein the gynecological tumors are hysteromyoma or cervical cancer.
  8. 8. The use of a tanshinone I intrauterine sustained release preparation for treating gynecological tumors according to any one of claims 1-7, wherein the biodegradable polymer sustained release stick is administered by intrauterine implantation.
  9. 9. The use of the tanshinone I in-utero slow-release preparation for treating gynecological tumors according to claim 8, wherein the half-inhibitory concentration of tanshinone I on gynecological tumor lesion cells is lower than the half-inhibitory concentration of tanshinone I on normal myometrial cells or normal cervical epithelial cells, and the selectivity index is greater than 2.

Description

Tanshinone I intrauterine sustained-release medicament for treating gynecological tumors and application thereof Technical Field The invention relates to an intrauterine slow-release medicament, in particular to a tanshinone I intrauterine slow-release medicament for treating gynecological tumors and application thereof. Background Gynecological tumors, particularly uterine fibroids, are common benign tumors that plague women of vast childbearing ages worldwide. Although surgical treatment (e.g., hysterectomy, myoma rejection) is the current mainstay, it is traumatic, can affect fertility function, and presents a risk of recurrence. Thus, the development of safe, effective, minimally invasive or non-invasive drug treatment protocols has been an important need in the clinical and scientific fields. Tanshinone I is a fat-soluble phenanthrenequinone compound extracted from traditional Chinese medicine radix salviae miltiorrhizae. Modern pharmacological studies prove that tanshinone I has definite anti-tumor activity, and the mechanism of tanshinone I relates to induction of tumor cell apoptosis, inhibition of cell proliferation and migration, regulation of relevant signal channels and the like. In particular, in vitro researches on hysteromyoma cells and cervical cancer cells, tanshinone I has good inhibition potential, which provides a theoretical basis for application of tanshinone I in gynecological tumor treatment. However, the clinical application of tanshinone I faces significant pharmaceutical challenges, first, the poor water solubility. Tanshinone I is hardly soluble in water, which makes it difficult to prepare into conventional injection or oral liquid with stable and high efficiency, and has low bioavailability. Second, targeting is lacking. If the medicine is prepared into common oral tablets or capsules, the effective concentration of the medicine at the focus (uterus) is limited after systemic absorption, and the systemic administration dosage has to be increased in order to achieve the therapeutic concentration, and unnecessary systemic exposure and potential toxic and side effects are increased. At present, clinical application dosage forms of tanshinone mainly concentrate on common injection, tablet and the like of tanshinone IIA, and the traditional dosage forms cannot solve the problems, and a tanshinone I preparation for uterus local administration is not found. Disclosure of Invention The invention overcomes the defects of the prior art and provides a tanshinone I intrauterine sustained-release medicament for treating gynecological tumors and application thereof. In order to achieve the aim, the invention adopts the technical proposal that the tanshinone I intrauterine sustained-release medicament for treating gynecological tumor and the application thereof comprise a tanshinone I nano-structure lipid carrier and a biodegradable polymer sustained-release rod for loading the tanshinone I nano-structure lipid carrier; wherein the tanshinone I nanostructured lipid carrier comprises tanshinone I with the average particle diameter of 100-200 nm, solid lipid and an emulsifier, and the encapsulation rate is not lower than 70%; The biodegradable polymer slow release rod is of a rod-shaped structure suitable for being placed in a uterine cavity, and can degrade and release the tanshinone I nanostructure lipid carrier under the environment of the uterine cavity, so that the local slow release of the medicine is realized. In a preferred embodiment of the present invention, the solid lipid is selected from one or more of glyceryl monostearate, glyceryl behenate and glyceryl stearate, and the emulsifier is selected from one or more of soybean lecithin, lecithin and poloxamer 188. In a preferred embodiment of the present invention, the tanshinone I nanostructure lipid carrier is prepared by a high-pressure homogenization method or a microemulsion method, and the Zeta potential is between-30 mV and-5 mV in the preparation process. In a preferred embodiment of the invention, the biodegradable polymer slow release rod is in a shape of a simulated uterus with the length of 30 mm-70 mm, the width of 30 mm-65 mm and the thickness of 0.1 mm-2 mm. In a preferred embodiment of the invention, the biodegradable polymer sustained-release rod comprises an outer coating formed by a degradable micro-nano fiber membrane loaded with a drug and an inner core membrane which is encapsulated in the outer coating and is prepared from a water-swellable biodegradable polymer material. In a preferred embodiment of the invention, the degradable micro-nano fiber membrane is prepared by adopting an electrostatic spinning technology, the material is one or more selected from polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone and degradable polyurethane, and the material of the inner core membrane is one or more selected from alginate, hyaluronic acid, chitosan and carboxymethyl chitosan. In a preferred embo